ORCID Profile
0000-0002-7211-4651
Current Organisation
Griffith University
Does something not look right? The information on this page has been harvested from data sources that may not be up to date. We continue to work with information providers to improve coverage and quality. To report an issue, use the Feedback Form.
Research Topics
In Research Link Australia (RLA), "Research Topics" refer to ANZSRC FOR and SEO codes. These topics are either sourced from ANZSRC FOR and SEO codes listed in researchers' related grants or generated by a large language model (LLM) based on their publications.
Top 5 Research Topics
ANZSRC Field of Research (FoR)
Biological Sciences Not Elsewhere Classified | Medical Biotechnology | Other Biological Sciences | Biomaterials | Specialist Studies in Education | Research, Science And Technology Policy | Regenerative Medicine (incl. Stem Cells and Tissue Engineering) | Cell Development, Proliferation and Death | Education Studies Not Elsewhere Classified
ANZSRC Socio-Economic Objective (SEO)
Health Related to Ageing | Expanding Knowledge in Engineering | Nervous system and disorders | Expanding Knowledge in the Biological Sciences | Higher education | Biological sciences |
Related Links
Publications
The α-Synuclein Gene and Parkinson Disease in a Chinese Population
Publisher: American Medical Association (AMA)
Date: 04-2000
DOI: 10.1001/ARCHNEUR.57.4.501
Abstract: To study the Ala53Thr and Ala30Pro mutations of the alpha-synuclein gene in a large number of Chinese patients with Parkinson disease (PD) as well as controls. We recruited 183 Chinese patients with sporadic PD, 17 with younger-onset PD (onset age <50 years), and 7 with PD and a positive family history as well as 227 unaffected Chinese control subjects from the outpatient departments of 2 major hospitals in Hong Kong. All subjects were assessed for the the diagnosis of PD by a consultant neurologist or geriatrician. Subjects were interviewed with a standard questionnaire that also questioned for family history. Venous blood s les were obtained from the subjects and genomic DNA was extracted and studied for the presence of Ala53Thr mutation in exon 4 and Ala30Pro mutation in exon 3 of the alpha-synuclein gene using a polymerase chain reaction restriction fragment length polymorphism method. None of the Chinese PD patients or controls had either the Ala53Thr (exon 4) or Ala30Pro (exon 3) mutation of the alpha-synuclein gene. We failed to discover Ala53Thr or Ala30Pro mutations in a large number of Chinese patients with PD and control subjects, adding to the emerging consensus that variations in the alpha-synuclein gene are associated with PD in few families worldwide.
Heterozygous PINK1 p.G411S increases risk of Parkinson’s disease via a dominant-negative mechanism
Publisher: Oxford University Press (OUP)
Date: 02-11-2016
DOI: 10.1093/BRAIN/AWW261
The disposition of aspirin and salicylic acid in the isolated perfused rat liver: The effect of normal and retrograde flow on availability and mean transit time
Publisher: Oxford University Press (OUP)
Date: 07-1996
DOI: 10.1111/J.2042-7158.1996.TB03962.X
Abstract: The effect of changing the direction of perfusate flow from anterograde to retrograde on the disposition of acetylsalicylic acid (aspirin) and salicylic acid was studied in the single pass in-situ perfused rat liver. Mixtures of aspirin, [14C]salicylic acid and the inert reference solute [3H]sucrose were administered as boluses into the liver using red blood cell and albumin-free perfusate media at a flow rate of 30 mL min−1/liver. Hepatic availability (F), mean transit time (MTT) and normalized variance (CV2) for aspirin, preformed [14C]salicylic acid, salicylic acid produced from aspirin in the liver and [3H]sucrose were deduced from the outflow concentration profiles using statistical moment analysis. The values for F, MTT and CV2 for the solutes under anterograde perfusion were: aspirin (0.73 ± 0.04, 15.13 ± 2.01 s, 0.33 ± 0.09, n = 5), preformed [14C]salicylic acid (1.05 ± 0.06, n=12, 43.19 ± 2.21 s, 1.08 ± 0.08, n = 5), salicylic acid from aspirin (0.33 ± 0.05, 42.82 ± 9.16 s, 0.73 ± 0.10, n = 5) and [3H]sucrose (1.05 ± 0.05, 16.88 ± 0.77 s, 0.74 ± 0.10, n = 5). The corresponding values for retrograde perfusions were: aspirin (0.73 ± 0.02, 17.41 ± 3.06 s, 0.32 ± 0.09, n = 5), preformed [14C]salicylic acid (1.14 ± 0.02, 44.42 ± 3.16 s, 0.95 ± 0.07, n = 5), salicylic acid from aspirin (0.33 ± 0.09, 36.47 ± 10.28 s, 0.58 ± 0.05, n = 5) and sucrose (1.01 ± 0.04, 18.08 ± 1.61 s, 0.76 ± 0.15, n = 5). No significant differences in F or MTT were apparent between anterograde and retrograde perfusions for all solutes. The MTT and CV2 data for [14C]salicylic acid and salicylic acid produced from aspirin is suggestive of a permeability limitation for salicylic acid transport.
Validity and reliability of the Geriatric Anxiety Inventory in Parkinson's disease*
Publisher: Wiley
Date: 29-12-2012
DOI: 10.1111/J.1741-6612.2010.00487.X
Abstract: To examine the psychometric properties of a novel anxiety rating scale, the Geriatric Anxiety Inventory (GAI) in Parkinson's disease (PD). The predictive validity of the GAI was tested against the presence of any DSM-IV anxiety disorders in 58 PD patients using receiver operating curve analysis. The concurrent validity of this scale was also studied against the state half of the Spielberger State Trait Anxiety Inventory (STAI). The internal consistency and test-retest reliability of the GAI were also examined. The GAI displayed good concurrent validity against the STAI and the DSM-IV. It also showed good internal consistency and test-retest reliability. This study suggested that the GAI is an appropriate scale to use in non-demented PD patients.
An isolated in-situ rat head perfusion model for pharmacokinetic studies
Publisher: Springer Science and Business Media LLC
Date: 2000
Abstract: To develop a viable, single pass rat head perfusion model useful for pharmacokinetic studies. A viable rat head preparation, perfused with MOPS-buffered Ringer's solution, was developed. Radiolabelled markers (red blood cells, water and sucrose) were injected in a bolus into the internal carotid artery and collected from the posterior facial vein over 28 minutes. The double inverse Gaussian function was used to estimate the statistical moments of the markers. The viability of the perfusion was up to one hour, with optimal perfusate being 2% bovine serum albumin at 37 degrees C, pH 7.4. The distribution volumes for red blood cells, sucrose and water (from all studies, n = 18) were 1.0 +/- 0.3 ml, 6.4 +/- 4.2 ml and 18.3 +/- 11.9 ml, respectively. A high normalised variance for red blood cells (3.1 +/- 2.0) suggests a marked vascular heterogeneity. A higher normalised variance for water (6.4 +/- 3.3) is consistent with additional diffusive ermeability limitations. Analysis of the physiological parameters derived from the moments suggested that the kinetics of the markers were consistent with distribution throughout the head (weight 25 g) rather than just the brain (weight 2 g). This model should assist in studying solute pharmacokinetics in the head.
A Grand Challenge. 3. Unbiased Phenotypic Function of Metabolites from Australia Plants Gloriosa superba and Alangium villosum against Parkinson's Disease
Publisher: American Chemical Society (ACS)
Date: 06-05-2020
STEM CELL MODELS FOR BIOMARKER DISCOVERY IN BRAIN DISEASE
Publisher: Elsevier
Date: 2011
Risk factors for idiopathic dystonia in Queensland, Australia
Publisher: Elsevier BV
Date: 12-2015
DOI: 10.1016/J.JOCN.2014.03.032
Abstract: It is currently hypothesised that a combination of genetic and environmental factors underlies the development of idiopathic isolated dystonia (IID). In this study, we examined several possible environmental or other non-genetic factors that may influence the risk for IID in Queensland, Australia. We surveyed several environmental exposures, lifestyle factors, medical and family histories to investigate potential risk factors for IID. Associations between putative risk factors and IID were assessed using a total of 184 dystonia patients and 1048 neurologically-normal control subjects s led from Queensland between 2005 and 2012. Our analyses revealed that anxiety disorders, depression, tremor, cigarette smoking and head injuries with a loss of consciousness were associated with increased risk for IID (p<0.05), all of which remained statistically significant following an adjustment for multiple hypothesis testing except for depression. We also observed that the risk for dystonia increased with higher cigarette smoking pack-year quartiles in our analyses. Our results suggest possible environmental factors that influence the development of IID and complement the findings of similar dystonia risk factor studies. Further investigation defining the environmental and other non-genetic risk factors for IID may provide insight into the development of the disorder in genetically-susceptible in iduals.
Assessment methods and factors associated with depression in Parkinson's disease
Publisher: Elsevier BV
Date: 11-2011
DOI: 10.1016/J.JNS.2011.06.031
Abstract: Depression is a common problem experienced by patients with Parkinson's disease (PD). Identifying depression in PD is difficult and the determinants of depression in PD are complex and debatable. Here we review our recent studies which have (i) examined the validity of current depression rating scales in PD, (ii) introduced a self-reported and validated strategy to identify a lifetime history of depression in PD, and (iii) investigated genetic and non-genetic factors associated with depression in the context of PD. Our research showed PD-specific cut-off values suitable to use for the Hamilton Depression Scales (HAMD and HDI) and the Geriatric Depression Scale (GDS-15) when dichotomising patients with and without a current depression. Using the GDS-15 specific cut-off scores and a number of self-reported questions that screen for a lifetime history of depression, we developed a novel method to dichotomise PD patients according to current depression or a past history of depression. This method was applied in a large-scale study examining the factors associated with depression in PD. We clarified that the severity of PD is positively related to depression. We also showed that a number of other clinical factors including a longer duration of PD, a younger PD onset age, frequent falls, a history of anxiety disorder and memory problems were associated with depression in PD. In addition to these clinical factors, we observed associations between depression, and lower education levels, a history of smoking and a regular use of non-aspirin bases NSAIDs or analgesics. No associations were found between depression in PD and common genetic variations examined across the serotonin and dopamine transporter genes. Our studies provide a focus for future intervention strategies.
α-Synuclein Aggregation Inhibitory Procerolides and Diphenylalkanes from the Ascidian Polycarpa procera
Publisher: American Chemical Society (ACS)
Date: 14-02-2023
The monoamine oxidase B gene GT repeat polymorphism and Parkinson's disease in a Chinese population
Publisher: Springer Science and Business Media LLC
Date: 17-01-2000
Abstract: Monoamine oxidase B (MAOB) metabolises dopamine and activates neurotoxins known to induce parkinsonism in humans and primates. Therefore the MAOB gene (MAOB Xp15.21-4) is a candidate gene for Parkinson's disease (PD). Longer length dinucleotide repeat sequences in a highly polymorphic GT repeat region of intron 2 of this gene showed an association with PD in an Australian cohort. We repeated this allele-association study in a population of 176 Chinese PD patients (90 men, 86 women) and 203 agematched controls (99 men, 104 women). Genomic DNA was extracted from venous blood and the polymerase chain reaction was used to lify the appropriate regions of the MAOB gene. The length of each (GT) repeat sequence was determined by 5% polyacrylamide denaturing gel electrophoresis. There was no significant difference in allele frequencies of the (GT) repeat allelic variation between patients and controls (chi2 = 2.48 df = 5, P<0.75). Therefore the longer length GT repeat alleles are not associated with PD in this Chinese population. Possible reasons for the discrepancy between Chinese and Australian populations include a different interaction between this genetic factor and environmental factors in the two populations and the possibility that the long length GT repeat alleles may represent a marker mutation, genetically linked to another susceptibility allele in whites but not in Chinese. Methodological differences in the ascertainment of cases and controls in this cohort could also explain the observed differences. Further study is required to determine whether the longer length GT repeat alleles are true susceptibility alleles in PD.
Hepatic structure‐pharmacokinetic relationships: The hepatic disposition and metabolite kinetics of a homologous series of O‐acyl derivatives of salicylic acid
Publisher: Wiley
Date: 08-1998
Paraoxonase polymorphisms, pesticide exposure and Parkinson's disease in a caucasian population
Publisher: Springer Science and Business Media LLC
Date: 11-08-2000
Abstract: Parkinson's disease (PD) has been associated with exposure to pesticides and oxidative injury. The involvement of paraoxonase in both pesticide metabolism and lipid peroxidation suggests that it may play a role in the pathogenesis of PD. We examined the frequency of polymorphic alleles of the PON1 and PON2 genes in a s le of caucasian subjects with PD. The frequency distribution of these genotypes did not differ significantly between patients and controls, including those who had reported exposure to pesticides.
Phytochemical investigation of Asarum sieboldii var. seoulense and the phenotypic profiles of its constituents against a Parkinson's Disease olfactory cell line
Publisher: Elsevier BV
Date: 08-2023
Rare POLG1 CAG variants do not influence Parkinson's disease or polymerase gamma function
Publisher: Elsevier BV
Date: 03-2014
DOI: 10.1016/J.MITO.2014.01.004
Abstract: A recent meta-analysis suggested that rare CAG repeat variants in the gene that encodes polymerase gamma (POLG1) predispose in iduals to develop Parkinson's disease (PD) alternative alleles were proposed to increase risk by 27%. In the current case-control study of 2255 Australians, we observed no statistical association between in iduals possessing rare CAG repeat genotypes and PD (p=0.178) a subsequent meta-analysis of 2852 PD cases and 2833 controls was also non-significant (OR=1.085, p=0.124). Moreover, mitochondrial DNA synthesis (p=0.427) or Complex I activity (p=0.639) were not different in cells derived from in iduals with different POLG1 genotypes. These data provide no evidence to suggest CAG repeat length in POLG1 affects PD susceptibility.
A novel screen for nuclear mitochondrial gene associations with Parkinson?s disease
Publisher: Springer Science and Business Media LLC
Date: 02-2004
DOI: 10.1007/S00702-003-0085-8
Abstract: Genetic factors play an important role in the aetiology of Parkinson's disease (PD). We have screened nuclear genes encoding subunits of mitochondrial complex I for associations between single nucleotide polymorphisms (SNPs) and PD. Abnormal functioning of complex I is well documented in human PD. Moreover, toxicological inhibition of complex I can lead to parkinsonism in animals. Thus, commonly occurring variants in these genes could potentially influence complex I function and the risk of developing PD. A sub-set of 70 potential SNPs in 31 nuclear complex I genes were selected and association analysis was performed on 306 PD patients plus 321 unaffected control subjects. Genotyping was performed using the DASH method. There was no evidence that the examined SNPs were significant genetic risk factors for PD, although this initial screen could not exclude the possibility that other disease-influencing variations exist within these genes.
O-GlcNAc Modification Protects against Protein Misfolding and Aggregation in Neurodegenerative Disease
Publisher: American Chemical Society (ACS)
Date: 15-04-2019
DOI: 10.1021/ACSCHEMNEURO.9B00143
Abstract: Post-translational modifications (PTMs) of proteins are becoming the focus of intense research due to their implications in a broad spectrum of neurodegenerative diseases. Various PTMs have been identified to alter the toxic profiles of proteins which play critical roles in disease etiology. In Alzheimer's disease (AD), dysregulated phosphorylation is reported to promote pathogenic processing of the microtubule-associated tau protein. Among the PTMs, the enzymatic addition of N-acetyl-d-glucosamine (GlcNAc) residues to Ser/Thr residues is reported to deliver protective effects against the pathogenic processing of both amyloid precursor protein (APP) and tau. Modification of tau with as few as one single O-GlcNAc residue inhibits its toxic self-assembly. This modification also has the same effect on the assembly of the Parkinson's disease (PD) associated α-synuclein (ASyn) protein. In fact, O-GlcNAcylation ( O-linked GlcNAc modification) affects the processing of numerous proteins implicated in AD, PD, amyotrophic lateral sclerosis (ALS), and Huntington's disease (HD) in a similar manner. As such, manipulation of a protein's O-GlcNAcylation status has been proposed to offer therapeutic routes toward addressing multiple neurodegenerative pathologies. Here we review the various effects that O-GlcNAc modification, and its modulated expression, have on pathogenically significant proteins involved in neurodegenerative disease.
GSK3B polymorphisms alter transcription and splicing in Parkinson's disease
Publisher: Wiley
Date: 28-11-2005
DOI: 10.1002/ANA.20691
Abstract: Parkinson's disease (PD) is a neurodegenerative disorder characterized by a combination of motor symptoms. We identified two functional single nucleotide polymorphisms in the glycogen synthase kinase-3beta gene (GSK3B). A promoter single nucleotide polymorphism (rs334558) is associated with transcriptional strength in vitro in which the T allele has greater activity. An intronic single nucleotide polymorphism (rs6438552) regulates selection of splice acceptor sites in vitro. The T allele is associated with altered splicing in lymphocytes and increased levels of GSK3B transcripts that lack exons 9 and 11 (GSKDeltaexon9+11). Increased levels of GSKDeltaexon9+11 correlated with enhanced phosphorylation of its substrate, Tau. In a comparison of PD and control brains, there was increased in frequency of T allele (rs6438552) and corresponding increase in GSKDeltaexon9+11 and Tau phosphorylation in PD brains. Conditional logistic regression indicated gene-gene interaction between T/T genotype of rs334558 and H1/H1 haplotype of microtubule-associated protein Tau (MAPT) gene (p = 0.009). There was association between a haplotype (T alleles of both GSK3B polymorphisms) and disease risk after stratification by Tau haplotypes ((H1/H2+H2/H2 in iduals: odds ratio, 1.64 p = 0.007 (H1/H1 in iduals: odds ratio, 0.68 p < 0.001). Ours results suggest GSK3B polymorphisms alter transcription and splicing and interact with Tau haplotypes to modify disease risk in PD.
Imagining an interdisciplinary doctoral pedagogy
Publisher: Informa UK Limited
Date: 07-2006
Anxiety disorders in Parkinson's disease: Prevalence and risk factors
Publisher: Wiley
Date: 13-04-2010
DOI: 10.1002/MDS.22833
Abstract: Anxiety disorders are common in Parkinson's disease (PD) patients, yet are poorly studied. We examined the prevalence of anxiety disorders in PD, investigated the association between anxiety, and presentation and progression of PD, and studied for the first time the contribution of putative risk factors for anxiety in PD. A case-series of 79 PD patients recruited from neurology out-patient clinics was examined for anxiety disorders using the DSM-IV criteria. The Unified Parkinson's Disease Rating Scale and the Hoehn and Yahr Staging of PD were employed to understand the relationship between anxiety disorders, and the clinical presentation and severity of PD. A validated survey assessed putative risk factors for anxiety in PD. Twenty-five percent of PD patients were diagnosed with anxiety. Panic disorder, generalised anxiety disorder and social phobia were prevalent anxiety disorders. Comorbid depression with anxiety was observed (14%). The severity but not the duration of PD was positively related to anxiety. PD patients with postural instability and gait dysfunction symptom clustering were more likely to experience anxiety than tremor-dominant patients. While levodopa dosage had no relationship to anxiety, experience of dyskinesias or on/off fluctuations increased the risk. Lateralisation of PD had no association with anxiety. Anxiety disorders decreased with age and young onset PD patients were more likely to experience anxiety than the late onset subjects. Anxiety adds to the complexity of PD, lowering patients' quality of life. Future research can be directed to identify reactive and organic nature of anxiety in PD.
Lack of replication of thirteen single-nucleotide polymorphisms implicated in Parkinson's disease: a large-scale international study
Publisher: Elsevier BV
Date: 11-2006
Genome-wide Association and Meta-analysis of Age at Onset in Parkinson Disease
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 16-08-2022
DOI: 10.1212/WNL.0000000000200699
Abstract: Considerable heterogeneity exists in the literature concerning genetic determinants of the age at onset (AAO) of Parkinson disease (PD), which could be attributed to a lack of well-powered replication cohorts. The previous largest genome-wide association studies (GWAS) identified SNCA and TMEM175 loci on chromosome (Chr) 4 with a significant influence on the AAO of PD these have not been independently replicated. This study aims to conduct a meta-analysis of GWAS of PD AAO and validate previously observed findings in worldwide populations. A meta-analysis was performed on PD AAO GWAS of 30 populations of predominantly European ancestry from the Comprehensive Unbiased Risk Factor Assessment for Genetics and Environment in Parkinson's Disease (COURAGE-PD) Consortium. This was followed by combining our study with the largest publicly available European ancestry dataset compiled by the International Parkinson Disease Genomics Consortium (IPDGC). The COURAGE-PD Consortium included a cohort of 8,535 patients with PD (91.9%: Europeans and 9.1%: East Asians). The average AAO in the COURAGE-PD dataset was 58.9 years (SD = 11.6), with an underrepresentation of females (40.2%). The heritability estimate for AAO in COURAGE-PD was 0.083 (SE = 0.057). None of the loci reached genome-wide significance ( p 5 × 10 −8 ). Nevertheless, the COURAGE-PD dataset confirmed the role of the previously published TMEM175 variant as a genetic determinant of the AAO of PD with Bonferroni-corrected nominal levels of significance ( p 0.025): (rs34311866: β(SE) COURAGE = 0.477(0.203), p COURAGE = 0.0185). The subsequent meta-analysis of COURAGE-PD and IPDGC datasets (N total = 25,950) led to the identification of 2 genome-wide significant association signals on Chr 4, including the previously reported SNCA locus (rs983361: β(SE) COURAGE+IPDGC = 0.720(0.122), p COURAGE+IPDGC = 3.13 × 10 −9 ) and a novel BST1 locus (rs4698412: β(SE) COURAGE+IPDGC = −0.526(0.096), p COURAGE+IPDGC = 4.41 × 10 −8 ). Our study further refines the genetic architecture of Chr 4 underlying the AAO of the PD phenotype through the identification of BST1 as a novel AAO PD locus. These findings open a new direction for the development of treatments to delay the onset of PD.
Modelling α-synuclein processing in primary patient cells for pharmacological intervention
Publisher: Open Exploration Publishing
Date: 25-10-2023
Sulfotransferase 1A3/4 copy number variation is associated with neurodegenerative disease
Publisher: Springer Science and Business Media LLC
Date: 04-04-2017
DOI: 10.1038/TPJ.2017.4
Abstract: The cytosolic aryl sulfotransferase genes SULT1A3 and SULT1A4 are located on chromosome 16p11.2 in a region of chromosomal instability. SULT1A3/4 are important enzymes in the metabolism of catecholamines linked to neurodegenerative diseases such as Parkinson's and Alzheimer's. In the present study, copy number variation of the SULT1A3/4 genes in healthy in iduals, as well as a cohort of Parkinson's disease and Alzheimer's disease patients was examined. In all subjects, SULT1A3/4 copy number varied from 1 to 10. In Alzheimer's disease patients, there was a significantly lower copy number compared to controls, and a positive correlation between copy number and age of disease onset. By contrast, there were no differences in Parkinson's disease patients. However, when early-onset Parkinson's disease was evaluated separately, there appeared to be an association with gene copy number and risk. The current study shows that these neurodegenerative diseases may be related to SULT1A3/4 copy number.
Induced pluripotent stem cell line (LCSBi001-A) derived from a patient with Parkinson's disease carrying the p.D620N mutation in VPS35
Publisher: Elsevier BV
Date: 05-2020
Improved nutritional status is related to improved quality of life in Parkinson's disease
Publisher: Springer Science and Business Media LLC
Date: 18-11-2014
A Cross-Study Transcriptional Analysis of Parkinson's Disease
Publisher: Public Library of Science (PLoS)
Date: 23-03-2009
Glutathione transferase Omega class polymorphisms in Parkinson disease
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 24-05-2004
Proteomic profiling of idiopathic Parkinson's disease primary patient cells by SWATH-MS
Publisher: Wiley
Date: 07-06-2022
Abstract: Parkinson's disease (PD) is the second most prevalent neurodegenerative disease. It is generally diagnosed clinically after the irreversible loss of dopaminergic neurons and no general biomarkers currently exist. To gain insight into the underlying cellular causes of PD we aimed to quantify the proteomic differences between healthy control and PD patient cells. Sequential Window Acquisition of all THeoretical Mass Spectra was performed on primary cells from healthy controls and PD patients. In total, 1948 proteins were quantified and 228 proteins were significantly differentially expressed in PD patient cells. In PD patient cells, we identified seven significantly increased proteins involved in the unfolded protein response (UPR) and focused on cells with high and low amounts of PDIA6 and HYOU1. We discovered that PD patients with high amounts of PDIA6 and HYOU1 proteins were more sensitive to endoplasmic reticulum stress, in particular to tunicamycin. Data is available via ProteomeXchange with identifier PXD030723. This data from primary patient cells has uncovered a critical role of the UPR in patients with PD and may provide insight to the underlying cellular dysfunctions in these patients.
Mini-review on initiatives to interfere with the propagation and clearance of alpha-synuclein in Parkinson’s disease
Publisher: Springer Science and Business Media LLC
Date: 12-2017
The serotonin transporter gene and Parkinson's disease
Publisher: S. Karger AG
Date: 2000
DOI: 10.1159/000008206
Abstract: Dysfunction in the serotonin (5-hydroxytryptamine) system and reduced serotonin concentrations have been reported in patients with Parkinson’s disease (PD). Serotonin concentrations in neural tissue are controlled by a presynaptic serotonin transporter protein that is encoded by a single gene. Therefore, we investigated whether a polymorphic region in the serotonin transporter gene is associated with PD. Three variable-number tandem repeat (VNTR) elements of the serotonin transporter gene were detected by polymerase chain reaction, those with 9, 10, 11 and 12 copies of the repeat element. The 10-copy VNTR element was significantly less common in patients with PD than controls in the univariate analysis (p 0.05). Logistic regression analysis revealed no significant differences between patients (n = 198) and controls (n = 200) in the distribution frequencies of 9- and 12-copy alleles and combined genotypes (odds ratio = 1.20 p = 1.71). A positive family history of PD was a strong predictor of disease risk (odds ratio = 2.98 95% confidence interval 1.51–5.87 p = 0.001). Although slight differences were observed between patient and control groups, these data suggest that defects in serotonin concentrations in patients with PD are unlikely to be due to polymorphisms in the serotonin transporter gene in this large Australian cohort however, the inverse association observed with the 10-copy allele warrants further investigation.
Genome-wide association study confirms BST1 and suggests a locus on 12q24 as the risk loci for Parkinson's disease in the European population
Publisher: Oxford University Press (OUP)
Date: 17-11-2010
DOI: 10.1093/HMG/DDQ497
Abstract: We performed a three-stage genome-wide association study (GWAS) to identify common Parkinson's disease (PD) risk variants in the European population. The initial genome-wide scan was conducted in a French s le of 1039 cases and 1984 controls, using almost 500 000 single nucleotide polymorphisms (SNPs). Two SNPs at SNCA were found to be associated with PD at the genome-wide significance level (P < 3 × 10(-8)). An additional set of promising and new association signals was identified and submitted for immediate replication in two independent case-control studies of subjects of European descent. We first carried out an in silico replication study using GWAS data from the WTCCC2 PD study s le (1705 cases, 5200 WTCCC controls). Nominally replicated SNPs were further genotyped in a third s le of 1527 cases and 1864 controls from France and Australia. We found converging evidence of association with PD on 12q24 (rs4964469, combined P = 2.4 × 10(-7)) and confirmed the association on 4p15/BST1 (rs4698412, combined P = 1.8 × 10(-6)), previously reported in Japanese data. The 12q24 locus includes RFX4, an isoform of which, named RFX4_v3, encodes brain-specific transcription factors that regulate many genes involved in brain morphogenesis and intracellular calcium homeostasis.
Factors associated with depression in Parkinson's disease
Publisher: Elsevier BV
Date: 07-2011
DOI: 10.1016/J.JAD.2011.01.021
Abstract: Depression is common in Parkinson's disease (PD) and contributes significantly to a reduced quality of life in PD patients. The determinants of depression in PD are complex and poorly understood. We investigated the factors associated with depression in PD. PD patients were recruited from Neurology clinics. A validated method was used to screen for a lifetime history of depression. 'Depressed' patients were identified by a score of >6 in the Geriatric Depression Scale (GDS-15) or by having had prescribed treatment for depression. 'Never depressed' patients were recognised by a score of <5 in the GDS-15 with no signs of a history of depression. A newly developed and validated questionnaire was used to collect other information. Depression was identified in 66% of the 639 PD patients who met the inclusion criteria. Depression was associated with an increased severity of illness as evidenced by higher Unified PD Rating Scale scores and a higher Hoehn and Yahr stage. Other clinical factors associated with disease severity were also more frequently observed in depressed patients. Similar to findings in non-PD s les, depressed PD patients were more likely to have a lower education level, a history of smoking and to regularly use non-aspirin based NSAIDs or analgesics. Comorbidities such as anxiety, memory problems, hallucinations, sleep disturbances and postural hypotension were more common in depressed PD patients. To avoid patient exhaustion of over-surveying, some factors within the psychological domain were not examined. Our results provide a focus for future intervention strategies.
Changes in pallidal neural activity following long-term symptom improvement from botulinum toxin treatment in DYT6 dystonia: a case report
Publisher: Springer Science and Business Media LLC
Date: 09-01-2022
DOI: 10.1186/S13256-021-03215-4
Abstract: The globus pallidus internus is the main target for the treatment of dystonia by deep brain stimulation. Unfortunately, for some genetic etiologies, the therapeutic outcome of dystonia is less predictable. In particular, therapeutic outcomes for deep brain stimulation in craniocervical and orolaryngeal dystonia in DYT6-positive patients are poor. Little is known about the neurophysiology of the globus pallidus internus in DYT6-positive dystonia, and how symptomatic treatment affects the neural activity of this region. We present here the case of a 55-year-old Caucasian female DYT6-dystonic patient with blepharospasm, spasmodic dysphonia, and oromandibular dystonia where single-unit and local field potential activity was recorded from the globus pallidus internus during two deep brain stimulation revision surgeries 4 years apart with no symptomatic improvement. Botulinum toxin injections consistently improved dysphonia, while some of the other symptoms were only inconsistently or marginally improved. Neural activity in the globus pallidus internus during both revision surgeries were compared with previously published results from an idiopathic dystonic cohort. Single-cell firing characteristics and local field potential from the first revision surgery showed no differences with our control group. However, during the second revision surgery, the mean firing rate of single units and local field potential power in the gamma range were lower than those present during the first revision surgery or the control group. Symptoms related to facial movements were greatly improved by botulinum toxin treatment between revision surgeries, which coincided with lower discharge rate and changes in gamma local field oscillations.
Potassium Channels in Parkinson's Disease: Potential Roles in its Pathogenesis and Innovative Molecular Targets for Treatment
Publisher: American Society for Pharmacology & Experimental Therapeutics (ASPET)
Date: 14-03-2023
GPNN: Power studies and applications of a neural network method for detecting gene-gene interactions in studies of human disease
Publisher: Springer Science and Business Media LLC
Date: 25-01-2006
Abstract: The identification and characterization of genes that influence the risk of common, complex multifactorial disease primarily through interactions with other genes and environmental factors remains a statistical and computational challenge in genetic epidemiology. We have previously introduced a genetic programming optimized neural network (GPNN) as a method for optimizing the architecture of a neural network to improve the identification of gene combinations associated with disease risk. The goal of this study was to evaluate the power of GPNN for identifying high-order gene-gene interactions. We were also interested in applying GPNN to a real data analysis in Parkinson's disease. We show that GPNN has high power to detect even relatively small genetic effects (2–3% heritability) in simulated data models involving two and three locus interactions. The limits of detection were reached under conditions with very small heritability ( %) or when interactions involved more than three loci. We tested GPNN on a real dataset comprised of Parkinson's disease cases and controls and found a two locus interaction between the DLST gene and sex. These results indicate that GPNN may be a useful pattern recognition approach for detecting gene-gene and gene-environment interactions.
Parkinson's disease: Alterations in iron and redox biology as a key to unlock therapeutic strategies
Publisher: Elsevier BV
Date: 05-2021
α-synuclein aggregation inhibitory activity of the bromotyrosine derivatives aerothionin and aerophobin-2 from the subtropical marine sponge Aplysinella sp
Publisher: Elsevier BV
Date: 2022
Lack of association between CYP1A1 polymorphism and Parkinson's disease in a Chinese population
Publisher: Springer Science and Business Media LLC
Date: 2002
Abstract: Apart from very few families who have a direct cause from genetic mutation, causes of most Parkinson's disease (PD) remain unclear. Many allelic association studies on polymorphism of different candidate genes have been studied. Although these association studies do not imply a causal relationship, it does warrant further studies to elucidate the pathophysiologic significance. CYP1A1 polymorphisms have been reported to be associated with PD in a Japanese population s le. Since CYP1A1 transforms aromatic hydrocarbons into products that may be neurotoxic and perhaps lead to PD, we therefore undertook a study to look at the possible association of CYP1A1 polymorphism and PD in a Chinese population. Contrary to the Japanese result, we did not find any statistically significant difference between the PD group and the control group in our study with a bigger s le size.
Australian Parkinson’s Genetics Study (APGS): pilot (n=1532)
Publisher: BMJ
Date: 02-2022
DOI: 10.1136/BMJOPEN-2021-052032
Abstract: Parkinson’s disease (PD) is a neurodegenerative disorder associated with progressive disability. While the precise aetiology is unknown, there is evidence of significant genetic and environmental influences on in idual risk. The Australian Parkinson’s Genetics Study seeks to study genetic and patient-reported data from a large cohort of in iduals with PD in Australia to understand the sociodemographic, genetic and environmental basis of PD susceptibility, symptoms and progression. In the pilot phase reported here, 1819 participants were recruited through assisted mailouts facilitated by Services Australia based on having three or more prescriptions for anti-PD medications in their Pharmaceutical Benefits Scheme records. The average age at the time of the questionnaire was 64±6 years. We collected patient-reported information and sociodemographic variables via an online (93% of the cohort) or paper-based (7%) questionnaire. One thousand five hundred and thirty-two participants (84.2%) met all inclusion criteria, and 1499 provided a DNA s le via traditional post. 65% of participants were men, and 92% identified as being of European descent. A previous traumatic brain injury was reported by 16% of participants and was correlated with a younger age of symptom onset. At the time of the questionnaire, constipation (36% of participants), depression (34%), anxiety (17%), melanoma (16%) and diabetes (10%) were the most reported comorbid conditions. We plan to recruit sex-matched and age-matched unaffected controls, genotype all participants and collect non-motor symptoms and cognitive function data. Future work will explore the role of genetic and environmental factors in the aetiology of PD susceptibility, onset, symptoms, and progression, including as part of international PD research consortia.
Identification of a New α-Synuclein Aggregation Inhibitor via Mass Spectrometry Based Screening
Publisher: American Chemical Society (ACS)
Date: 22-05-2019
DOI: 10.1021/ACSCHEMNEURO.9B00092
Abstract: The aggregation of disordered α-synuclein protein is pathogenically connected with Parkinson's disease. Therefore, discovering molecules that can inhibit the misfolding and aggregation of α-synuclein is an active research area in PD drug development. A key property of such required therapeutic agents is specific binding to the target protein. Mass spectrometry allows rapid detection of direct interactions between molecules and proteins and is an ideal technique for discovering specific α-synuclein binders. Here, by setting up an automated mass spectrometry-based screening system, we were able to screen over 2500 compounds and identify a new α-synuclein inhibitor, 3-[(3-methoxyphenyl)carbamoyl]-7-[( E)-2-phenylethenyl]-4,7-dihydropyrazolo [1,5- a]pyrimidine-5-carboxylic acid (compound 2). This compound not only significantly inhibits the misfolding and aggregation of α-synuclein and protects neuroblastoma cells from α-synuclein toxicity, but also has a more specific binding site compared with positive controls. Our work for the first time reports the inhibition of compound 2 on α-synuclein aggregation and also consolidates the capability of mass spectrometry to discover α-synuclein aggregation inhibitors.
An Ensemble Approach to Modelling the Combined Effect of Risk Factors on Age at Parkinson’s Disease Onset
Publisher: Springer International Publishing
Date: 2020
Teaching NeuroImages: Neuroferritinopathy
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 31-10-2011
Common polymorphisms in dystonia-linked genes and susceptibility to the sporadic primary dystonias
Publisher: Elsevier BV
Date: 05-2012
DOI: 10.1016/J.PARKRELDIS.2011.11.024
Abstract: Genes involved in familial dystonia syndromes (DYT genes) are ideal candidates for investigating whether common genetic variants influence the susceptibility to sporadic primary dystonia. To date, there have been few candidate gene studies for primary dystonia and only two DYT genes, TOR1A and THAP1, have been assessed. We therefore employed a haplotype-tagging strategy to comprehensively assess if common polymorphisms in eight DYT genes (TOR1A, TAF1, GCH1, THAP1, MR-1 (PNKD), SGCE, ATP1A3 and PRKRA) confer risk for sporadic primary dystonia. The 230 primary dystonia cases were matched for age and gender to 228 controls, recruited from movement disorder clinics in Brisbane, Australia and the Australian electoral roll. All subjects were genotyped for 56 tagging SNPs and genotype associations were investigated. Modest genotypic associations (P<0.05) were observed for three GCH1 SNPs (rs12147422, rs3759664 and rs10483639) when comparing all cases against controls. Associations were also seen when the cases were stratified based on presentation. Overall, our findings do not support the hypothesis that common TOR1A variants affect susceptibility for sporadic primary dystonia, and that it is unlikely that common variants around the DYT genes confer substantial risk for sporadic primary dystonia. Further work is warranted to follow up the GCH1 SNPs and the subgroup analyses.
Factors related to sleep disturbances for individuals with Parkinson’s disease: a regional perspective
Publisher: Cambridge University Press (CUP)
Date: 23-09-2019
DOI: 10.1017/S1041610219001212
Abstract: Sleep disturbances negatively impact the quality of life of patients with Parkinson’s disease (PD). While persons living in regional areas are at higher risk of PD, PD is poorly managed in regional communities. This study examined factors associated with sleep problems in PD in a regional context. A mixed-methods cross-sectional design was used. Patients with PD were recruited from the Queensland Parkinson’s Project database. Those who agreed to participate were sent a questionnaire assessing aspects of sleep, depression, anxiety, quality of life, and PD severity. Qualitative information was also gathered. Correlations between variables were examined thematic analyses were performed for qualitative data. All participants (n = 49) reported sleep disturbances, with 73% (n = 36) reporting sleep disturbance to be problematic. Global sleep dysfunction positively correlated with daytime napping (r = .34, p = .01), watching the clock when unable to sleep (r = .38, p = .01), staying in bed when unable to sleep (r = .43, p = .01), and going to bed hungry (r = .31, p = .03) and negatively correlated with daytime exercise (r = -.32, p = .02). Positive correlations were observed between global sleep dysfunction and depression (r = .55, p = .01), anxiety (r = .31, p = .04), and dysfunctional sleep beliefs (r = .39, p = .01). There is a clear need for identifying factors related to sleep disturbances in PD for effective management.
Pipeline to gene discovery - Analysing familial Parkinsonism in the Queensland Parkinson's Project
Publisher: Elsevier BV
Date: 04-2018
DOI: 10.1016/J.PARKRELDIS.2017.12.033
Abstract: Family based study designs provide an informative resource to identify disease-causing mutations. The Queensland Parkinson's Project (QPP) has been involved in numerous genetic screening studies however, details of the families enrolled into the register have not been comprehensively reported. This article characterises the families enrolled in the QPP and summarises monogenic forms of hereditary Parkinsonism found in the register. The presence of pathogenic point mutations and copy number variations (CNVs) were, generally, screened in a s le of over 1000 PD patients from the total of 1725. Whole exome sequencing (WES) was performed on eighteen probands from multiplex families. The QPP contains seventeen incidences of confirmed monogenic forms of PD, including LRRK2 p.G2019S, VPS35 p.D620N, SNCA duplications and PARK2 p.G430D (hom) & exon 4 deletion (hom). Of these seventeen, five belong to multi-incident families, while another eight have a family history of at least one other case of PD. In additional families, WES did not identify known forms of monogenic Parkinsonism however, three heterozygous mutations in PARK2, p.R275W, p.Q34fs, and a 40bp deletion in exon 3 were identified. Of these three mutations, only the 40bp deletion segregated with disease in a dominant inheritance pattern. Eighteen probands have screened negative for known CNVs and mutations that cause clear monogenic forms of PD. Each family is a candidate for further genetic analysis to identify genetic variants segregating with disease. The families enrolled in the QPP provide a useful resource to aid in identifying novel forms of monogenic PD.
Pooled analysis of iron-related genes in Parkinson's disease: Association with transferrin
Publisher: Elsevier BV
Date: 02-2014
Impulse-response studies on tracer doses of [C-14]lignocaine and its multiple metabolites in the perfused rat liver
Publisher: Oxford University Press (OUP)
Date: 10-1997
DOI: 10.1111/J.2042-7158.1997.TB06033.X
Abstract: The outflow-concentration-time profiles for lignocaine (lidocaine) and its metabolites have been measured after bolus impulse administration of [14C]lignocaine into the perfused rat liver. Livers from female Sprague-Dawley rats were perfused in a once-through fashion with red-blood-cell-free Krebs-Henseleit buffer containing 0 or 2% bovine serum albumin. Perfusate flow rates of 20 and 30 mL min− were used and both normal and retrograde flow directions were employed. Significant amounts of metabolite were detected in the effluent perfusate soon after lignocaine injection. The early appearance of metabolite contributed to bimodal outflow profiles observed for total 14C radioactivity. The lignocaine outflow profiles were well characterized by the two-compartment dispersion model, with efflux rate «influx rate. The profiles for lignocaine metabolites were also characterized in terms of a simplified two-compartment dispersion model. Lignocaine was found to be extensively metabolized under the experimental conditions with the hepatic availability ranging between 0.09 and 0.18. Generally lignocaine and metabolite availability showed no significant change with alterations in perfusate flow rate from 20 to 30 mL min− or protein content from 0 to 2%. A significant increase in lignocaine availability occurred when 1200 μm unlabelled lignocaine was added to the perfusate. Solute mean transit times generally decreased with increasing flow rate and with increasing perfusate protein content. The results confirm that lignocaine pharmacokinetics in the liver closely follow the predictions of the well-stirred model. The increase in lignocaine availability when 1200 μm unlabelled lignocaine was added to the perfusate is consistent with saturation of the hydroxylation metabolic pathways of lignocaine metabolism.
Australian data and meta-analysis lend support for alpha-synuclein (NACP-Rep1) as a risk factor for Parkinson's disease
Publisher: Elsevier BV
Date: 02-2005
DOI: 10.1016/J.NEULET.2004.10.078
Abstract: It remains unclear whether genetic variants in SNCA (the alpha-synuclein gene) alter risk for sporadic Parkinson's disease (PD). The polymorphic mixed sequence repeat (NACP-Rep1) in the promoter region of SNCA has been previously examined as a potential susceptibility factor for PD with conflicting results. We report genotype and allele distributions at this locus from 369 PD cases and 370 control subjects of European Australian ancestry, with alleles designated as -1, 0, +1, +2, and +3 as previously described. Allele frequencies designated (0) were less common in Australian cases compared to controls (OR=0.80, 95% CI 0.62-1.03). Combined analysis including all previously published ancestral European Rep1 data yielded a highly significant association between the 0 allele and a reduced risk for PD (OR=0.79, 95% CI 0.70-0.89, p=0.0001). Further study must now proceed to examine in detail this interesting and biologically plausible genetic association.
Association study of the NEDD9 gene with the risk of developing Alzheimer's and Parkinson's disease
Publisher: Oxford University Press (OUP)
Date: 25-06-2008
DOI: 10.1093/HMG/DDN183
Abstract: Alzheimer's disease (AD) and Parkinson's disease (PD), the two most common neurodegenerative disorders in the elderly, have been hypothesized to share genetic determinants. Recently, Li et al. proposed that a variant in the NEDD9 gene may be one of these common genetic factors. We attempted to confirm this initial observation by conducting an equivalent analysis in terms of pathologies and s le size. We genotyped the NEDD9 rs760678 SNP in three independent AD case-control studies (n = 3176) and two independent PD case-control studies (n = 1855). However, we failed to detect an association of this SNP with the risk of developing AD or PD, in any of these populations. In conclusion, these data indicate that the rs760678 SNP of the NEDD9 gene is at best a weak genetic determinant of AD or PD.
Parkinson's disease and family history
Publisher: Elsevier BV
Date: 10-2006
DOI: 10.1016/J.PARKRELDIS.2006.03.002
Abstract: The study of family history in Parkinson's disease (PD) has resulted in considerable debate over the role of genetic factors in the development of PD. Despite this, family history is consistently identified as an independent risk factor for PD. A multifactorial disease process in which genetic, environmental and lifestyle factors culminate in overall risk seems most likely. This article reviews existing studies of familial aggregation in PD. Recent insights into rare genetic causes of PD have affirmed the importance of ongoing family history research. Future efforts should emphasise well-designed family studies with extensive, non-exclusive phenotyping and ideally long-term follow-up.
Singing for people with Parkinson's disease
Publisher: Wiley
Date: 26-02-2019
α-Synuclein binding activity of the plant growth promoter asterubine
Publisher: Elsevier BV
Date: 05-2022
DOI: 10.1016/J.BMCL.2022.128677
Abstract: Preventing the aggregation of certain amyloid proteins has the potential to slow down the progression of diseases like Alzheimer's, Parkinson's, and type 2 diabetes mellitus. During a high-throughput screen of 300 Australian marine invertebrate extracts, the extract of the marine sponge Thorectandra sp. 4408 displayed binding activity to the Parkinson's disease-associated protein, α-synuclein. Isolation of the active component led to its identification as the known plant growth promoter asterubine (1). This molecule shares distinct structural similarities with potent amyloid beta aggregation inhibitors tramiprosate (homotaurine) and ALZ-801. Herein we report the isolation, NMR data acquired in DMSO and α-synuclein binding activity of asterubine (1).
No evidence of increased risk of colorectal cancer in individuals heterozygous for the Cys282Tyr haemochromatosis mutation
Publisher: Wiley
Date: 12-1999
DOI: 10.1046/J.1440-1746.1999.02027.X
Abstract: Previous studies have suggested that increased body iron stores and heterozygosity for haemochromatosis are associated with an increased risk of colorectal carcinoma. The aim of this study is to determine if there is an association between (i) colorectal carcinoma and heterozygosity for the Cys282Tyr mutation of the haemochromatosis gene (HFE) and (ii) this mutation and tumour site or stage. Two hundred and twenty-nine unselected patients (127 males, 102 females, mean age 68.0 years) with sporadic colorectal carcinoma and 228 controls (145 males, 83 females, mean age 69.7 years) were studied. DNA was tested for the presence of the Cys282Tyr mutation by digestion with Rsa1 and fragments separated by electrophoresis. Twenty-one patients with colorectal cancer and 23 control subjects were heterozygous for the Cys282Tyr mutation of HFE (relative risk 0.90). There was no association between heterozygosity of the Cys282Tyr mutation and tumour site or stage. Heterozygosity for the Cys282Tyr mutation of HFE does not appear to be a risk factor for colorectal carcinoma.
Prevalence of smell loss in Parkinson's disease - A multicenter study
Publisher: Elsevier BV
Date: 08-2009
DOI: 10.1016/J.PARKRELDIS.2008.12.005
Abstract: Previous data on the prevalence of olfactory dysfunction in Parkinson's disease (PD) range from 45% to 90%. The present multicenter study aimed to provide data on the prevalence of smell loss in a large s le of PD patients from three independent populations. Olfactory sensitivity was tested in 400 patients from Australia, Germany, and The Netherlands by means of a psychophysical olfactory test, the "Sniffin' Sticks", which is comprised of 3 subtests of olfactory function. Out of the total number of patients 45.0% presented as functionally anosmic, 51.7% were hyposmic, whereas only 3.3% were normosmic. This indicates that 96.7% of PD patients present with significant olfactory loss when compared to young normosmic subjects. This figure falls to 74.5%, however, when adjusted to age-related norms. Thus, olfactory dysfunction should be considered as a reliable marker of the disease.
Knowledge and attitudes towards genetic testing in those affected with Parkinson’s disease
Publisher: Springer Science and Business Media LLC
Date: 10-09-2013
Haplotype analysis of the IGF2-INS-TH gene cluster in Parkinson's disease
Publisher: Wiley
Date: 20-05-2008
DOI: 10.1002/AJMG.B.30633
Abstract: Idiopathic Parkinson's disease is a common movement disorder characterized by a loss of dopaminergic neurons in the substantia nigra. Its pathogenesis is postulated to involve complex interactions between genetic susceptibility and environmental exposures. The IGF2-INS-TH gene cluster on the telomeric end of human chromosome 11 is a gene rich region expressing several proteins important for dopamine neuron homeostasis. We used a haplotyping approach to determine whether common genetic variation in the IGF2-INS-TH cluster influences the risk of idiopathic Parkinson's disease in a Caucasian case-control group recruited from Brisbane, Australia. Three tagging polymorphisms, the SNPs, rs680 and rs689 and the microsatellite, HUMTH01, were genotyped in 215 cases and 215 age- and gender-matched controls. Eight common haplotypes accounted for 91% of the genetic variation in our control group and one haplotype, IGF2-INS-TH*6, was significantly under-represented among the cases with idiopathic Parkinson's disease (OR = 0.42, 95% CI = 0.25-0.72, P-value = 0.001). Analysis of the in idual polymorphisms showed that the IGF2-rs680 alternate 'A' allele accounted for the majority of the protective effect. Our findings suggest that common genetic variants in the IGF2-INS-TH cluster modify susceptibility to idiopathic Parkinson's disease.
Global investigation and meta-analysis of the C9orf72 (G4C2)n repeat in Parkinson disease
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 17-10-2014
Do Polymorphisms in the Familial Parkinsonism Genes Contribute to Risk for Sporadic Parkinson's Disease?
Publisher: Wiley
Date: 17-02-2009
DOI: 10.1002/MDS.22214
Abstract: Recent whole genome association studies provided little evidence that polymorphisms at the familial Parkinsonism loci influence the risk for Parkinson's disease (PD). However, these studies are not designed to detect the types of subtle effects that common variants may impose. Here, we use an alternative targeted candidate gene approach to examine common variation in 11 genes related to familial Parkinsonism. PD cases (n = 331) and unaffected control subjects (n = 296) were recruited from three specialist movement disorder clinics in Brisbane, Australia and the Australian Electoral Roll. Common genetic variables (76 SNPs and 1 STR) were assessed in all subjects and haplotype, genotype, and allele associations explored. Modest associations (uncorrected P < 0.05) were observed for common variants around SNCA, UCHL1, MAPT, and LRRK2 although none were of sufficient magnitude to survive strict statistical corrections for multiple comparisons. No associations were seen for PRKN, PINK1, GBA, ATP13A2, HTRA2, NR4A2, and DJ1. Our findings suggest that common genetic variables of selected PD-related loci contribute modestly to PD risk in Australians.
Calcium channels and iron metabolism: A redox catastrophe in Parkinson's disease and an innovative path to novel therapies?
Publisher: Elsevier BV
Date: 11-2021
Screening PARK genes for mutations in early-onset Parkinson's disease patients from Queensland, Australia
Publisher: Elsevier BV
Date: 02-2009
DOI: 10.1016/J.PARKRELDIS.2007.11.016
Abstract: A family history of Parkinson's disease (PD) is the most commonly reported risk factor after age, suggesting a genetic component to the disease in a sub-group of patients. Mutations in at least six genes have been identified that can lead to monogenic forms of PD. We screened a s le of 74 early-onset PD cases out of a cohort of 950 patients (onset <50 years) for genetic abnormalities in known familial Parkinsonism genes. A self-reported family history of PD existed for 30 patients (40.5%). Of these, 13 each had a first- or a second-degree relative with PD and four reported a more distant relative with PD. The entire coding region of the PRKN (MIM 602544), DJ-1 (MIM 602533) and PINK1 (MIM 698309) genes, and exon 41 of the LRRK2 gene (MIM 609007) were screened by direct sequencing. All exons of PRKN were examined for gene-dosage abnormalities. Screening identified five patients with putative genetic disease: two patients carried PRKN mutations (p.G12R heterozygous and p.G430D homozygous), one patient carried a p.G411S heterozygous amino acid change in the PINK1 gene and two in iduals were heterozygous for the common p.G2019S mutation in LRRK2. No alpha-synuclein or DJ-1 variants were observed. Our data suggest that approximately 7% of early-onset PD cases seen in Queensland movement disorders clinics have mutations involving known PARK genes.
Markers of Disease Severity Are Associated with Malnutrition in Parkinson's Disease
Publisher: Public Library of Science (PLoS)
Date: 27-03-2013
Alpha‐synuclein repeat variants and survival in Parkinson's disease
Publisher: Wiley
Date: 27-02-2014
DOI: 10.1002/MDS.25841
Design, Synthesis, and Biological Evaluation of Bimodal Glycopeptides as Inhibitors of Neurotoxic Protein Aggregation
Publisher: MDPI
Date: 07-08-2019
Different pieces of the same puzzle: a multifaceted perspective on the complex biological basis of Parkinson’s disease
Publisher: Springer Science and Business Media LLC
Date: 13-07-2023
DOI: 10.1038/S41531-023-00535-8
Abstract: The biological basis of the neurodegenerative movement disorder, Parkinson’s disease (PD), is still unclear despite it being ‘discovered’ over 200 years ago in Western Medicine. Based on current PD knowledge, there are widely varying theories as to its pathobiology. The aim of this article was to explore some of these different theories by summarizing the viewpoints of laboratory and clinician scientists in the PD field, on the biological basis of the disease. To achieve this aim, we posed this question to thirteen “PD experts” from six continents (for global representation) and collated their personal opinions into this article. The views were varied, ranging from toxin exposure as a PD trigger, to LRRK2 as a potential root cause, to toxic alpha-synuclein being the most important etiological contributor. Notably, there was also growing recognition that the definition of PD as a single disease should be reconsidered, perhaps each with its own unique pathobiology and treatment regimen.
Focused antithrombotic therapy: Novel anti-platelet salicylates with reduced ulcerogenic potential and higher first-pass detoxification than aspirin in rats
Publisher: Elsevier BV
Date: 12-1998
DOI: 10.1016/S0022-2143(98)90124-X
Abstract: The use of aspirin as an anti-platelet drug is limited by its propensity to induce gastric injury and by its adverse effect on vascular prostacyclin formation. Two phenolic non-steroidal anti-inflammatory drugs (salicylic acid and diflunisal) were modified by esterification with a series of O-acyl moieties. The short-term ulcerogenic in vitro and in vivo anti-platelet properties, pharmacodynamic profiles, and extent of hepatic extraction of these phenolic esters were compared with aspirin (acetylsalicylic acid). The more lipophilic esters (longer carbon chain length in O-acyl group) show significantly less gastrotoxicity in stressed rats than does aspirin after a single oral dose. The in vitro and in vivo anti-platelet studies show that these phenolic esters inhibited (1) arachidonate-triggered human platelet aggregation and (2) thrombin-stimulated rat serum thromboxane A2 production by platelets in the clotting process almost as effectively as aspirin. The hepatic extractions of these O-acyl derivatives are significantly higher than those of aspirin. The pharmacodynamic studies show that these O-acyl derivatives of salicylic acid and diflunisal probably bind to, or combine with, the same site on the platelet cyclooxygenase as aspirin. Replacing the O-acetyl group with longer chain O-acyl moiety in this series of phenolic esters markedly reduced the potential of these agents to induce short-term gastric injury but did not lessen their activity as inhibitors of platelet aggregation. These non-acetyl salicylates may therefore represent a novel class of anti-platelet drugs with less ulcerogenic potential.
Establishing an online resource to facilitate global collaboration and inclusion of underrepresented populations: Experience from the MJFF Global Genetic Parkinson’s Disease Project
Publisher: Public Library of Science (PLoS)
Date: 03-10-2023
Rapid subthalamic nucleus deep brain stimulation lead placement utilising CT/MRI fusion, microelectrode recording and test stimulation
Publisher: Springer Vienna
Date: 2006
DOI: 10.1007/978-3-211-35205-2_9
Abstract: Subthalamic nucleus (STN) deep brain stimulation (DBS) has become an established treatment strategy for patients with medically refractory Parkinson's disease (PD). There are however numerous strategies employed for STN lead placement. Variations include method of STN localisation, use of microelectrode recording, number of microelectrode recording passes and time taken for the procedure. We describe a relatively simple and rapid technique of STN lead placement utilising CT/ MRI image fusion, microelectrode recording and test stimulation. The first 58 consecutive patients undergoing STN DBS were assessed pre- and post-operatively. UPDRS scores, medication use and any surgical complication were assessed. Bilateral STN DBS was an efficacious treatment option for medically refractory PD. We have described a technique which can be performed with effect and low morbidity, and in a time which is well tolerated by patients.
Variance of Gene Expression Identifies Altered Network Constraints in Neurological Disease
Publisher: Public Library of Science (PLoS)
Date: 11-08-2011
Genetic Analysis of RAB39B in an Early-Onset Parkinson's Disease Cohort
Publisher: Frontiers Media SA
Date: 26-06-2020
The Vps35 D620N mutation linked to Parkinson's disease disrupts the cargo sorting function of retromer.
Publisher: Wiley
Date: 14-11-2014
DOI: 10.1111/TRA.12136
Abstract: The retromer is a trimeric cargo-recognition protein complex composed of Vps26, Vps29 and Vps35 associated with protein trafficking within endosomes. Recently, a pathogenic point mutation within the Vps35 subunit (D620N) was linked to the manifestation of Parkinson's disease (PD). Here, we investigated details underlying the molecular mechanism by which the D620N mutation in Vps35 modulates retromer function, including examination of retromer's subcellular localization and its capacity to sort cargo. We show that expression of the PD-linked Vps35 D620N mutant redistributes retromer-positive endosomes to a perinuclear subcellular localization and that these endosomes are enlarged in both model cell lines and fibroblasts isolated from a PD patient. Vps35 D620N is correctly folded and binds Vps29 and Vps26A with the same affinity as wild-type Vps35. While PD-linked point mutant Vps35 D620N interacts with the cation-independent mannose-6-phosphate receptor (CI-M6PR), a known retromer cargo, we find that its expression disrupts the trafficking of cathepsin D, a CI-M6PR ligand and protease responsible for degradation of α-synuclein, a causative agent of PD. In summary, we find that the expression of Vps35 D620N leads to endosomal alterations and trafficking defects that may partly explain its action in PD.
The Interaction between HLA‐DRB1 and Smoking in Parkinson's Disease Revisited
Publisher: Wiley
Date: 10-07-2022
DOI: 10.1002/MDS.29133
Abstract: Two studies that examined the interaction between HLA‐DRB1 and smoking in Parkinson's disease (PD) yielded findings in opposite directions. To perform a large‐scale independent replication of the HLA‐DRB1 × smoking interaction. We genotyped 182 single nucleotide polymorphism (SNPs) associated with smoking initiation in 12 424 cases and 9480 controls to perform a Mendelian randomization (MR) analysis in strata defined by HLA‐DRB1 . At the amino acid level, a valine at position 11 (V11) in HLA‐DRB1 displayed the strongest association with PD. MR showed an inverse association between genetically predicted smoking initiation and PD only in absence of V11 (odds ratio, 0.74, 95% confidence interval, 0.59–0.93, P Interaction = 0.028). In silico predictions of the influence of V11 and smoking‐induced modifications of α‐synuclein on binding affinity showed findings consistent with this interaction pattern. Despite being one of the most robust findings in PD research, the mechanisms underlying the inverse association between smoking and PD remain unknown. Our findings may help better understand this association. © 2022 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society
Parkinson's disease in relation to pesticide exposure and nuclear encoded mitochondrial complex I gene variants
Publisher: Hindawi Limited
Date: 2006
Abstract: Parkinson's disease (PD) is a common age-related neurodegenerative disorder thought to result from the integrated effects of genetic background and exposure to neuronal toxins. Certain in idual nuclear-encoded mitochondrial complex I gene polymorphisms were found to be associated with ∼ 2 -fold risk variation in an Australian case-control s le. We further characterized this s le of 306 cases and 321 controls to determine the mutual information contained in the 22 SNPs and, additionally, level of pesticide exposure: five distinct risk sets were identified using grade-of-membership analysis. Of these, one was robust to pesticide exposure (I), three were vulnerable (II, III, IV), and another (V) denoted low risk for unexposed persons. Risk for in idual subjects varied 16 -fold according to level of membership in the vulnerable groups. We conclude that inherited variation in mitochondrial complex I genes and pesticide exposure together modulate risk for PD.
Neuroferritinopathy
Publisher: Elsevier BV
Date: 09-2012
DOI: 10.1016/J.PARKRELDIS.2012.06.021
Abstract: Neuroferritinopathy is an autosomal dominantly inherited disorder caused by mutations in the gene encoding the ferritin light chain polypeptide. It leads to iron deposition particularly in the cerebellum, basal ganglia and motor cortex. The disease becomes clinically apparent in adulthood mainly with extrapyramidal signs and progresses slowly over decades. Patients usually have intact cognition until the very late stages of this disorder. Neuroimaging is the most helpful investigation and shows a very distinctive picture. So far no medication has been shown to have a disease-modifying effect. We present five new cases of this condition and review the current understanding of the pathogenesis and its clinical findings.
The Cys282Tyr polymorphism in the HFE gene in Australian Parkinson's disease patients
Publisher: Elsevier BV
Date: 07-2002
DOI: 10.1016/S0304-3940(02)00398-1
Abstract: Iron homeostasis is altered in Parkinson's disease (PD). The HFE protein is an important regulator of cellular iron homeostasis and variations within this gene can result in iron overload and the disorder known as hereditary haemochromatosis. We studied the Cys282Tyr single nucleotide polymorphism as a genetic risk factor for PD in two distinct and separately collected cohorts of Australian PD patients and controls. In the combined cohort comprising 438 PD patients and 485 control subjects, we revealed an odds ratio for possession of the 282Tyr allele of 0.61 (95% confidence interval, CI=0.42-0.90, P=0.011) from univariate chi-squared and 0.59 (95% CI=0.39-0.90, P=0.014) after logistic regression analyses (correcting for potential confounding factors). These results suggest that possession of the 282Tyr allele may offer some protection against the development of PD.
Surfactant protein expression in human skin: evidence and implications.
Publisher: Elsevier BV
Date: 02-2007
Abstract: The presence of surfactant proteins (SPs), critical to local barrier and defense functions and usually associated with the lung, was revealed in adult and fetal human skin complementary deoxyribonucleic acid, in skin s les from three adult female donors and also in cultured fibroblasts, keratinocytes, and melanocytes. Using reverse transcription-PCR, SP-A, SP-B, SP-C, and SP-D messenger ribonucleic acid expression was detected to varying extents in the different skin sources. The stronger expression of SP-C in fetal skin, compared to adult skin, suggested that the role of this protein alters with age. Immunohistochemical studies showed variable distribution of SPs in human epidermis and dermis, confirming that these proteins are indeed translated and expressed in skin tissue. In vitro studies showed that the surface tension of SP-deficient artificial sebum is (a) lowered by skin-extracted SP-B and (b) further reduced to a level comparable to normal sebum by the additional presence of skin-extracted SP-A and SP-D, consistent with their surface tension-lowering capabilities in lung. The possible roles of SPs in skin, based on their known functions in the lung are discussed. However, their potential as therapeutic targets or diagnostic markers of skin disease remains to be elucidated.
Chemical constituents from Macleaya cordata (Willd) R. Br. and their phenotypic functions against a Parkinson’s disease patient-derived cell line
Publisher: Elsevier BV
Date: 11-2020
The ubiquitin carboxy-terminal hydrolase-L1 gene S18Y polymorphism does not confer protection against idiopathic Parkinson's disease
Publisher: Elsevier BV
Date: 10-2000
DOI: 10.1016/S0304-3940(00)01510-X
Abstract: The ubiquitin carboxy-terminal hydrolase L1gene (UCH-L1) has been implicated in the aetiology of Parkinson's disease (PD). A rare Ile93Met mutation in UCH-L1 in a German PD sib-pair has been reported. Recently, a S18Y (C54A) polymorphism in exon 3 of UCH-L1 was found to be under-represented in PD patients compared to controls. To test the reproducibility of this negative association, we conducted an allele-association study of the S18Y polymorphism in an Australian case-control s le consisting of 142 PD cases and 142 closely matched control subjects. Genotypes were determined using polymerase chain reaction and RsaI restriction enzyme assay. Analysis revealed no significant difference between PD patients and controls for genotype or allele frequencies of the S18Y polymorphism. The frequency of the S18Y allele in Australian subjects is similar to that reported elsewhere. This study suggests that the S18Y polymorphism in UCH-L1 does not influence the risk for developing PD.
Meta-analysis of genome-wide DNA methylation identifies shared associations across neurodegenerative disorders
Publisher: Springer Science and Business Media LLC
Date: 26-03-2021
DOI: 10.1186/S13059-021-02275-5
Abstract: People with neurodegenerative disorders show erse clinical syndromes, genetic heterogeneity, and distinct brain pathological changes, but studies report overlap between these features. DNA methylation (DNAm) provides a way to explore this overlap and heterogeneity as it is determined by the combined effects of genetic variation and the environment. In this study, we aim to identify shared blood DNAm differences between controls and people with Alzheimer’s disease, amyotrophic lateral sclerosis, and Parkinson’s disease. We use a mixed-linear model method (MOMENT) that accounts for the effect of (un)known confounders, to test for the association of each DNAm site with each disorder. While only three probes are found to be genome-wide significant in each MOMENT association analysis of amyotrophic lateral sclerosis and Parkinson’s disease (and none with Alzheimer’s disease), a fixed-effects meta-analysis of the three disorders results in 12 genome-wide significant differentially methylated positions. Predicted immune cell-type proportions are disrupted across all neurodegenerative disorders. Protein inflammatory markers are correlated with profile sum-scores derived from disease-associated immune cell-type proportions in a healthy aging cohort. In contrast, they are not correlated with MOMENT DNAm-derived profile sum-scores, calculated using effect sizes of the 12 differentially methylated positions as weights. We identify shared differentially methylated positions in whole blood between neurodegenerative disorders that point to shared pathogenic mechanisms. These shared differentially methylated positions may reflect causes or consequences of disease, but they are unlikely to reflect cell-type proportion differences.
Sycosterol A, an α-Synuclein Inhibitory Sterol from the Australian Ascidian Sycozoa cerebriformis
Publisher: American Chemical Society (ACS)
Date: 17-11-2021
DOI: 10.1021/ACS.JNATPROD.1C00768
Abstract: During a recent biodiscovery study to identify new α-synuclein (α-syn) aggregation inhibitors, we screened 29 Australian marine sponge and ascidian extracts in an MS binding assay. This resulted in an extract from the ascidian
Does a rare mutation in PTPRA contribute to the development of Parkinson’s disease in an Australian multi-incident family?
Publisher: Public Library of Science (PLoS)
Date: 28-07-2022
DOI: 10.1371/JOURNAL.PONE.0271499
Abstract: The genetic study of multi-incident families is a powerful tool to investigate genetic contributions to the development of Parkinson’s disease. In this study, we identified the rare PTPRA p.R223W variant as one of three putative genetic factors potentially contributing to disease in an Australian family with incomplete penetrance. Whole exome sequencing identified these mutations in three affected cousins. The rare PTPRA missense variant was predicted to be damaging and was absent from 3,842 alleles from PD cases. Overexpression of the wild-type RPTPα and R223W mutant in HEK293T cells identified that the R223W mutation did not impair RPTPα expression levels or alter its trafficking to the plasma membrane. The R223W mutation did alter proteolytic processing of RPTPα, resulting in the accumulation of a cleavage product. The mutation also resulted in decreased activation of Src family kinases. The functional consequences of this variant, either alone or in concert with the other identified genetic variants, highlights that even minor changes in normal cellular function may increase the risk of developing PD.
Improved precision of epigenetic clock estimates across tissues and its implication for biological ageing
Publisher: Springer Science and Business Media LLC
Date: 23-08-2019
A Rare Case of Green Gelatinous Mass Formation on a Deep Brain Stimulation Implantable Pulse Generator.
Publisher: The Korean Movement Disorder Society
Date: 31-01-2020
DOI: 10.14802/JMD.20050
Hunting for Familial Parkinson’s Disease Mutations in the Post Genome Era
Publisher: MDPI AG
Date: 17-03-2021
Abstract: Parkinson’s disease (PD) is typically sporadic however, multi-incident families provide a powerful platform to discover novel genetic forms of disease. Their identification supports deciphering molecular processes leading to disease and may inform of new therapeutic targets. The LRRK2 p.G2019S mutation causes PD in 42.5–68% of carriers by the age of 80 years. We hypothesise similarly intermediately penetrant mutations may present in multi-incident families with a generally strong family history of disease. We have analysed six multiplex families for missense variants using whole exome sequencing to find 32 rare heterozygous mutations shared amongst affected members. Included in these mutations was the KCNJ15 p.R28C variant, identified in five affected members of the same family, two elderly unaffected members of the same family, and two unrelated PD cases. Additionally, the SIPA1L1 p.R236Q variant was identified in three related affected members and an unrelated familial case. While the evidence presented here is not sufficient to assign causality to these rare variants, it does provide novel candidates for hypothesis testing in other modestly sized families with a strong family history. Future analysis will include characterisation of functional consequences and assessment of carriers in other familial cases.
Parkinson's disease, MAOB, and smoking
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 08-1999
TNF gene polymorphism and quantitative traits related to cardiovascular disease: getting to the heart of the matter
Publisher: Springer Science and Business Media LLC
Date: 21-03-2007
Screening for rare sequence variants in the THAP1 gene in a primary dystonia cohort
Publisher: Wiley
Date: 06-05-2013
DOI: 10.1002/MDS.25479
Psychiatric disorders in idiopathic-isolated focal dystonia
Publisher: Springer Science and Business Media LLC
Date: 22-01-2014
DOI: 10.1007/S00415-014-7244-8
Abstract: Idiopathic-isolated focal dystonia (IIFD) is a movement disorder characterised by involuntary, sustained muscle contractions, leading to abnormal postures. Psychopathology is frequent in patients with IIFD, and while traditionally this was thought to be a secondary phenomenon, there is emerging evidence for shared neurobiological mechanisms. We conducted a single-centre cross-sectional study of 103 consecutive patients with IIFD and two comparison groups: 78 consecutive patients with hemifacial spasm (HFS) and 93 healthy control subjects. Assessments with regard to psychiatric disturbances were performed using self-report questionnaires, including the self-report version of the Yale-Brown Obsessive Compulsive Scale (Y-BOCS-SR), the Beck Anxiety Inventory (BAI), and the Beck Depression Inventory (BDI). Compared to healthy control subjects and patients with HFS, the IIFD group had higher OCS, anxiety, and depression scores as measured by the Y-BOCS-SR, BAI, and BDI, respectively. The Y-BOCS-SR, BAI, and BDI were highly correlated across all the subjects. Logistic regression analysis showed that the main driver of high obsessive-compulsive symptom scores, irrespective of neurological diagnosis, was the BDI, whereas it was BAI (and not BDI), that drives the association between the psychiatric rating scale scores and the neurological diagnosis. Our findings suggest that while clinically significant obsessive-compulsive symptoms are over-represented in IIFD patients relative to controls, the BAI may have better discriminatory power to distinguish between the psychiatric symptoms in IIFD patients.
Structure-hepatic disposition relationships for phenolic compounds
Publisher: Elsevier BV
Date: 07-1999
Age-environment and gene-environment interactions in the pathogenesis of Parkinson's disease
Publisher: Walter de Gruyter GmbH
Date: 2002
DOI: 10.1515/REVEH.2002.17.1.51
Abstract: Parkinson's disease (PD) is a common neurodegenerative disease characterized by dopaminergic cell death and deposition of Lewy bodies within the substantia nigra of the midbrain. Although the major risk factors for PD are aging and environmental factors, there is an important genetic component. An age-related change in xenobiotic metabolism alters the metabolism of and net exposure to, environmental neurotoxins. Genetic variability in xenobiotic metabolism may similarly increase the susceptibility to PD by altering the metabolism of neurotoxins. Genetic studies of rare familial cases of PD indicate a central mechanistic role for the aggregation of alpha-synuclein, a protein found in Lewy bodies. Environmental factors like pesticides and heavy metals can also influence alpha-synuclein aggregation. Common final pathways for aging, environmental, and genetic mechanisms can thus exist, involving both direct neurotoxicity and alpha-synuclein aggregation.
Evidence of a Recessively Inherited CCN3 Mutation as a Rare Cause of Early-Onset Parkinsonism
Publisher: Frontiers Media SA
Date: 15-05-2020
Large-scale assessment of polyglutamine repeat expansions in Parkinson disease
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 09-09-2015
Genetic and environmental risk factors and their interactions for Parkinson's disease in a Chinese population (vol 10, pg 313, 2003)
Publisher: Elsevier BV
Date: 02-2004
Exploiting the potential of molecular profiling in Parkinson's disease: current practice and future probabilities
Publisher: Informa UK Limited
Date: 11-2010
DOI: 10.1586/ERM.10.86
Abstract: Parkinson's disease (PD) is a common, heterogeneous syndrome diagnosed clinically by the presence of classical neurological symptoms and the absence of 'red flags' that suggest alternative secondary parkinsonian disorders. Neuropathologically, nigrostriatal loss and the presence of proteinaceous inclusions (Lewy bodies) confirm the diagnosis. For PD, molecular profiling promises much but is yet to deliver in terms of breakthroughs for identifying at-risk in iduals, detecting disease at early stages, improving diagnostic certainty, prognosticating future outcomes or providing surrogate markers of therapeutic efficacy. Recent, large-scale omics studies, driven by technological advances, have generated terabytes of data but not yet met the goal of developing biomarkers suitable for clinical use in PD. In this article we critically evaluate the recent literature to identify the key roadblocks and realistic opportunities facing researchers interested in utilizing molecular profiling in the clinic to improve the diagnosis and treatment of PD.
Dairy Intake and Parkinson's Disease: A Mendelian Randomization Study
Publisher: Wiley
Date: 08-01-2022
DOI: 10.1002/MDS.28902
Abstract: Previous prospective studies highlighted dairy intake as a risk factor for Parkinson's disease (PD), particularly in men. It is unclear whether this association is causal or explained by reverse causation or confounding. The aim is to examine the association between genetically predicted dairy intake and PD using two‐s le Mendelian randomization (MR). We genotyped a well‐established instrumental variable for dairy intake located in the lactase gene (rs4988235) within the Courage‐PD consortium (23 studies 9823 patients and 8376 controls of European ancestry). Based on a dominant model, there was an association between genetic predisposition toward higher dairy intake and PD (odds ratio [OR] per one serving per day = 1.70, 95% confidence interval = 1.12–2.60, P = 0.013) that was restricted to men (OR = 2.50 [1.37–4.56], P = 0.003 P ‐difference with women = 0.029). Using MR, our findings provide further support for a causal relationship between dairy intake and higher PD risk, not biased by confounding or reverse causation. Further studies are needed to elucidate the underlying mechanisms. © 2022 International Parkinson and Movement Disorder Society
The ACE Deletion Polymorphism Is Not Associated with Parkinson’s Disease
Publisher: S. Karger AG
Date: 1999
DOI: 10.1159/000008012
Abstract: The deletion allele (D allele) polymorphism in the angiotensin converting enzyme (ACE) gene is associated with increased levels of the neuropeptide substance P in the basal ganglia and substantia nigra. A reduction of substance P levels in the brain occurs in Parkinson’s disease (PD) and has been implicated in the pathogenesis of the disease. We investigated the hypothesis that the D allele may be protective towards PD by examining the frequency of the ACE (I/D) polymorphism in 178 PD cases (male:female ratio = 1.4) and 192 controls (male:female ratio = 1.5). ACE (I/D) genotype was determined using polymerase chain reaction and 3% agarose gel electrophoresis. Unadjusted chi-square analysis revealed no significant difference between genotype frequencies (χ sup /sup = 3.30, p 0.10) or allele frequencies (χ sup /sup = 2.52, p 0.10) between patient and control groups, although PD patients were less likely to be homozygous (OR = 0.80, 95% CI = 0.49–1.29) or heterozygous (OR = 0.80, 95% CI = 0.59–1.06) for the D allele. A stepwise logistic regression analysis of the ACE deletion and risk factor data confirmed that there was no significant association between the ACE deletion (D allele) polymorphism and PD (OR = 0.62, 95% CI = 0.35–1.10, p = 0.10). This study does not support the hypothesis that the D allele of the ACE gene confers a protective effect with respect to PD.
Embracing Monogenic Parkinson's Disease: The MJFF Global Genetic PD Cohort
Publisher: Wiley
Date: 24-01-2023
DOI: 10.1002/MDS.29288
Abstract: As gene‐targeted therapies are increasingly being developed for Parkinson's disease (PD), identifying and characterizing carriers of specific genetic pathogenic variants is imperative. Only a small fraction of the estimated number of subjects with monogenic PD worldwide are currently represented in the literature and availability of clinical data and clinical trial‐ready cohorts is limited. The objectives are to (1) establish an international cohort of affected and unaffected in iduals with PD‐linked variants (2) provide harmonized and quality‐controlled clinical characterization data for each included in idual and (3) further promote collaboration of researchers in the field of monogenic PD. We conducted a worldwide, systematic online survey to collect in idual‐level data on in iduals with PD‐linked variants in SNCA , LRRK2 , VPS35 , PRKN , PINK1 , DJ‐1 , as well as selected pathogenic and risk variants in GBA and corresponding demographic, clinical, and genetic data. All registered cases underwent thorough quality checks, and pathogenicity scoring of the variants and genotype–phenotype relationships were analyzed. We collected 3888 variant carriers for our analyses, reported by 92 centers (42 countries) worldwide. Of the included in iduals, 3185 had a diagnosis of PD (ie, 1306 LRRK2 , 115 SNCA , 23 VPS35 , 429 PRKN , 75 PINK1 , 13 DJ‐1 , and 1224 GBA ) and 703 were unaffected (ie, 328 LRRK2 , 32 SNCA , 3 VPS35 , 1 PRKN , 1 PINK1 , and 338 GBA ). In total, we identified 269 different pathogenic variants 1322 in iduals in our cohort (34%) were indicated as not previously published. Within the MJFF Global Genetic PD Study Group, we (1) established the largest international cohort of affected and unaffected in iduals carrying PD‐linked variants (2) provide harmonized and quality‐controlled clinical and genetic data for each included in idual (3) promote collaboration in the field of genetic PD with a view toward clinical and genetic stratification of patients for gene‐targeted clinical trials. © 2023 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.
UCHL1 is a Parkinson's disease susceptibility gene
Publisher: Wiley
Date: 21-03-2004
DOI: 10.1002/ANA.20017
Abstract: The reported inverse association between the S18Y variant of the ubiquitin carboxy-terminal hydrolase L1 (UCHL1) gene and Parkinson's disease (PD) has strong biological plausibility. If confirmed, genetic association of this variant with PD may support molecular targeting of the UCHL1 gene and its product as a therapeutic strategy for PD. In this light, we performed a collaborative pooled analysis of in idual-level data from all 11 published studies of the UCHL1 S18Y gene variant and PD. There were 1,970 cases and 2,224 unrelated controls. We found a statistically significant inverse association of S18Y with PD. Carriers of the variant allele (Y/Y plus Y/S vs S/S) had an odds ratio (OR) of 0.84 (95% confidence interval [CI], 0.73-0.95) and homozygotes for the variant allele (Y/Y vs S/S plus Y/S) had an OR of 0.71 (95% CI, 0.57-0.88). There was a linear trend in the log OR consistent with a gene dose effect (p = 0.01). The inverse association was most apparent for young cases compared with young controls. There was no evidence for publication bias and the associations remained significant after excluding the first published, hypothesis-generating study. These findings confirm that UCHL1 is a susceptibility gene for PD and a potential target for disease-modifying therapies.
Evidence for the role of FMR1 gray zone alleles as a risk factor for parkinsonism in females
Publisher: Wiley
Date: 07-2018
DOI: 10.1002/MDS.27420
Mutations in RAB39B cause X-linked intellectual disability and early-onset parkinson disease with α-synuclein pathology
Publisher: Elsevier BV
Date: 12-2014
Anti-prion and α-Synuclein Aggregation Inhibitory Sterols from the Sponge Lamellodysidea cf. chlorea
Publisher: American Chemical Society (ACS)
Date: 03-12-2020
Mapping of the PDQ-39 to EQ-5D scores in patients with Parkinson’s disease
Publisher: Springer Science and Business Media LLC
Date: 11-07-2012
DOI: 10.1007/S11136-012-0231-6
Abstract: The EuroQoL (EQ-5D) is ideal to compare quality of life across conditions. However, the Parkinson's Disease Questionnaire (PDQ-39) is often the only quality-of-life instrument used in Parkinson's disease research. We aimed to identify associations between PDQ-39 domains and EQ-5D domains, and compare different methods of developing a function to map the PDQ-39 to EQ-5D scores. Adults with Parkinson's disease self-completed both instruments. Ordinal regression identified associations between PDQ-39 domain scores and each EQ-5D domain. Modeling (n = 80) and validation sets (n = 16) were randomly generated. Overall performance of four methods of mapping the PDQ-39 to EQ-5D scores (using PDQ-39 domains and total score in ordinal and linear regression) was assessed with the validation set, followed by assessing the equivalence of observed and predicted EQ-5D scores on the full dataset controlling for sociodemographic factors. Different sets of PDQ-39 domains were associated with each EQ-5D domain. For ex le, PDQ-39 "Activities of Daily Living" and "Social Support" were associated with EQ-5D "Personal Care," while PDQ-39 "Emotional Well-being" was associated with EQ-5D "Anxiety/Depression." Over one-third (37.5 %) of predictions from ordinal regressions had an error <0.01 % (compared to 6.3 % for linear regressions). The EQ-5D scores predicted with ordinal regression using PDQ-39 domains were similar in distribution and association with sociodemographic factors to the observed EQ-5D scores. Of the four methods tested, using PDQ-39 domains in ordinal regression was superior for mapping EQ-5D scores. The function reported here may prove particularly useful for cost-utility analyses comparing Parkinson's disease with other conditions.
Caffeine and Parkinson's disease: are we getting our fix on risk-modifying gene-environment interactions?
Publisher: Wiley
Date: 31-01-2011
Role of the VPS35 D620N mutation in Parkinson's disease
Publisher: Elsevier BV
Date: 03-2017
DOI: 10.1016/J.PARKRELDIS.2016.12.001
Abstract: Parkinson's disease (PD) is a neurodegenerative disorder involving the loss of dopaminergic neurons in the brain. Following the discovery of the PD-causing D620N mutation in the VPS35 (Vacuolar sorting protein 35) gene, dysfunction in the subcellular retromer complex has been strongly implicated in pathogenesis of PD. Although the function and dysfunction of the retromer has been a focus of study for some time, the role of this complex in the development of PD is not fully understood. Investigating cellular alterations that occur when the retromer is rendered dysfunctional, such as when the D620N disease-causing mutation is introduced into various model systems, shows that endosomal processing defects are major contributors to the disease phenotype. Altered trafficking of retromer cargo molecules, reduced cellular survival and altered processing of alpha-synuclein have all been observed in the presence of the D620N mutation. In addition, interactions between the retromer and the protein products of other familial Parkinsonism-related genes, has made the retromer a prime target of research in PD. This review gives an overview of the changes in retromer function, identified thus far, that may contribute to the neurodegeneration observed in PD.
Association of APOE with Parkinson disease age-at-onset in women
Publisher: Elsevier BV
Date: 2007
DOI: 10.1016/J.NEULET.2006.07.080
Abstract: APOE polymorphism has received extensive attention as a risk factor for Parkinson's disease (PD), but findings have been equivocal. Analysis of APOE variants in an Australian PD case-control s le revealed a robust association between genotype and age-at-onset (AAO) of PD in women (P=0.0008). These data not only further implicate APOE in PD, but also provide a stark ex le of the effects that gender may play in complex disorders.
α-Synuclein Aggregation Inhibitory and Antiplasmodial Activity of Constituents from the Australian Tree Eucalyptus cloeziana
Publisher: American Chemical Society (ACS)
Date: 23-08-2023
Developing professional researchers: Research students' graduate attributes
Publisher: Informa UK Limited
Date: 03-2007
Comprehensive assessment of genetic sequence variants in the antioxidant 'master regulator' Nrf2 in idiopathic parkinson's disease
Publisher: Public Library of Science (PLoS)
Date: 26-05-2015
The role of the endolysosomal pathway in α-synuclein pathogenesis in Parkinson’s disease
Publisher: Frontiers Media SA
Date: 10-01-2023
DOI: 10.3389/FNCEL.2022.1081426
Abstract: Parkinson’s disease (PD) is a chronic neurodegenerative disease that is characterized by a loss of dopaminergic neurons in the substantia nigra pars compacta of the midbrain (SNpc). Extensive studies into genetic and cellular models of PD implicate protein trafficking as a prominent contributor to the death of these dopaminergic neurons. Considerable evidence also suggests the involvement of α-synuclein as a central component of the characteristic cell death in PD and it is a major structural constituent of proteinaceous inclusion bodies (Lewy bodies LB). α-synuclein research has been a vital part of PD research in recent years, with newly discovered evidence suggesting that α-synuclein can propagate through the brain via prion-like mechanisms. Healthy cells can internalize toxic α-synuclein species and seed endogenous α-synuclein to form large, pathogenic aggregates and form LBs. A better understanding of how α-synuclein can propagate, enter and be cleared from the cell is vital for therapeutic strategies.
Novel Furan-2-yl-1 H-pyrazoles Possess Inhibitory Activity against α-Synuclein Aggregation
Publisher: American Chemical Society (ACS)
Date: 18-06-2020
Lack of reproducibility in re-evaluating associations between GCH1 polymorphisms and Parkinson's disease and isolated dystonia in an Australian case-control group
Publisher: Elsevier BV
Date: 06-2014
Subcortical Activity During Verbal Selection and Suppression in Parkinson's Disease
Publisher: Elsevier BV
Date: 10-2012
N400 and Emotional word processing in Parkinson's disease
Publisher: American Psychological Association (APA)
Date: 09-2017
DOI: 10.1037/NEU0000333
Abstract: Emotional and cognitive disturbances are common complications in Parkinson's disease (PD). N400 is an event related potential (ERP) strongly linked to lexical-semantic processing and has demonstrated alterations in litude and latency when PD patients performed semantic priming tasks. The present study investigated the role of N400 in an automatic affective priming paradigm in PD. Other ERP components relevant to emotion processing were also examined. Twenty-two PD patients and 17 healthy adults performed an automatic affective priming task while ERPs were recorded using 128 channels. Prime-target word pairs of negative or neutral valence were presented at a stimulus onset asynchrony of 250 ms. Participants were asked to evaluate the valence of the target word by button press. A larger N400 litude for incongruent compared with congruent neutral targets was observed at right central and parietal regions and did not differ between PD and controls. PD and controls also displayed larger P300 and late positive potential (LPP) litudes for negative compared with neutral targets at central parietal and right frontal regions. In contrast, whereas controls showed a larger slow negative wave (SNW) for negative targets compared with neutral targets at left frontal and left central regions, PD group demonstrated a significant reduction in SNW litude difference at the left central region. N400 is intact in PD when processing evaluative judgments of emotional words. P300 and LPP were also intact in PD. The altered left central SNW in PD suggests an ERP marker for emotional dysfunction in PD. (PsycINFO Database Record
Depression symptomatology correlates with event-related potentials in Parkinson's disease: An affective priming study
Publisher: Elsevier BV
Date: 02-2019
DOI: 10.1016/J.JAD.2018.11.094
Abstract: Depression is a predominant non-motor symptom of Parkinson's disease (PD), which is often under recognised and undertreated. To improve identification of depression in PD it is imperative to examine objective brain-related markers. The present study addresses this gap by using electroencephalography (EEG) to evaluate the processing of emotionally valanced words in PD. Fifty non-demented PD patients, unmedicated for depression or anxiety, completed an affective priming task while EEG was simultaneously recorded. Prime and target word pairs of negative or neutral valence were presented at a short 250 ms stimulus onset asynchrony. Participants were asked to evaluate the valence of the target word by button press. Depression was measured using an established rating scale. Repeated measures analysis of covariance and correlational analyses were performed to examine whether event-related potentials (ERP) varied as a function of depression scores. Key ERP findings reveal reduced responses in parietal midline P300, N400 and Late Positive Potential (LPP) difference waves between congruent and incongruent neutral targets in patients with higher depression scores. Comparisons of ERPs were limited by insufficient classification of participants with and without clinical depression. A majority of PD patients who had high depression scores were excluded from the analysis as they were receiving antidepressant and/or anxiolytic medications which could interfere with ERP sensitivity. The present study suggests that the Pz-P300, N400 and LPP are ERP markers relates to emotional dysfunction in PD. These findings thus advance current knowledge regarding the neurophysiological markers of a common neuropsychiatric deficit in PD.
Glutathione transferase polymorphism and Parkinson's disease - Reply
Publisher: Elsevier BV
Date: 1999
Validity of Hamilton depression inventory in Parkinson's disease
Publisher: Wiley
Date: 2007
DOI: 10.1002/MDS.21309
Abstract: Studies investigating the assessment of depression in Parkinson's disease (PD) are limited. We examined the concurrent validity and the internal consistency of the Hamilton Depression Inventory (HDI) and compared it to the Hamilton and Geriatric Depression Scales. PD patients (n = 79) were recruited from neurology clinics. Diagnosis of depressive disorder was made according to DSM-IV criteria. Receiver operating characteristic curves were used to calculate sensitivity, specificity, and positive and negative predictive values. The HDI exhibited an optimal cutoff for discriminating between depressed and nondepressed PD patients of 13.5/14.0 and is a valid instrument to use in the setting of PD.
Zeta class glutathione transferase polymorphisms and Parkinson's disease [2]
Publisher: BMJ
Date: 03-2001
Sequence variation in the proximity of IDE may impact age at onset of both Parkinson disease and Alzheimer disease
Publisher: Springer Science and Business Media LLC
Date: 06-2004
DOI: 10.1007/S10048-004-0173-4
Abstract: We recently reported that a linkage disequilibrium (LD) block on chromosome 10q encompassing the gene encoding insulin-degrading enzyme ( IDE) harbors sequence variants that associate with Alzheimer disease (AD). Evidence also indicated effects upon a number of quantitative indices of AD severity, including age-at-onset (AAO). Since linkage of this immediate region to AAO has been shown in both AD and Parkinson disease (PD), we have explored the possibility that polymorphism within this LD block might also influence PD. Utilizing single nucleotide polymorphisms that delineate common haplotypes from this region, we observed significant evidence of association with AAO in an Australian PD case-control s le. Analyses were complemented with AAO data from two independent Swedish AD case s les, for which previously reported findings were replicated. Results were consistent between AD and PD, suggesting the presence of equivalent detrimental and protective alleles. These data highlight a genomic region in the proximity of IDE that may contribute to AD and PD in a similar manner.
Utility of a patient survey in identifying fluctuations in early stage Parkinson’s disease
Publisher: Elsevier BV
Date: 11-2008
DOI: 10.1016/J.JOCN.2007.09.018
Abstract: Motor and non-motor fluctuations are well known sequelae of dopaminergic therapies for Parkinson's disease (PD), particularly during the advanced stages. However, the prevalence of fluctuations early in the treatment course has been less well recognised and may be missed clinically if not specifically probed. We examined the used of a survey for this purpose. Patients to be surveyed were recruited by neurologists and geriatricians at 20 Australian centres. Patients had a diagnosis of idiopathic PD with a duration of fewer than 5 years and were considered by their treating physician to be non-fluctuating or had no change in their treatment plan in the prior 6 months. Patients, with or without assistance, completed a 19-item wearing-off questionnaire to assess the presence of motor and non-motor fluctuations that indicated early wearing-off. Investigators assessed the usefulness of the questionnaire in detecting fluctuations and guiding PD treatment. Of 105 patients recruited, 92 were eligible for analysis. There were 56 (61%) identified as having fluctuations. Patients with wearing-off were younger (mean 67 vs 72 years), and more likely to have had PD for more than 3 years. About half the patients (49%) were able to complete the questionnaire independently. Clinicians perceived the questionnaire as useful for detecting fluctuations and adjusting treatment. A simple and easily administered wearing-off questionnaire may be useful in the early detection of fluctuations in PD patients and assist in guiding therapy.
Further evidence that interactions between CYP2D6 and pesticide exposure increase risk for Parkinson's disease
Publisher: Wiley
Date: 27-05-2004
DOI: 10.1002/ANA.20143
Nrf2: a modulator of Parkinson’s disease?
Publisher: Springer Science and Business Media LLC
Date: 04-05-2016
DOI: 10.1007/S00702-016-1563-0
Abstract: Parkinson's disease (PD) is a complex multifactorial disorder that has been associated with the processes of oxidative stress. In the absence of curative therapies, modification of the neurodegenerative process-including the manipulation of endogenous antioxidant pathways-is the focus of intensive research. Recently, genetic and pharmacological accretion of the transcription factor, and phase II antioxidant 'master regulator' Nrf2, has shown to demonstrably mitigate the toxic neuronal effects of parkinsonian agents such as MPP(+), rotenone, and hydrogen peroxide in vitro and in vivo. Furthermore, baseline genetic variability in Nrf2-dependant pathways may promote neuronal susceptibility to exogenous agents and correlate with PD onset within certain populations. While contemporary evidence directly implicating Nrf2 in the pathogenesis of PD is not conclusive and likely contingent upon the evaluation of complex interacting factors-including genetic variation and a history of environmental exposures-it remains a promising target for therapeutic benefit in the modulation of oxidative stress.
Nonsteroidal Anti‐inflammatory Use and LRRK2 Parkinson's Disease Penetrance
Publisher: Wiley
Date: 14-07-2020
DOI: 10.1002/MDS.28189
Nutrition screening and assessment in Parkinson's disease: Acomparison of methods
Publisher: Elsevier BV
Date: 10-2013
Analysis of DNA methylation associates the cystine–glutamate antiporter SLC7A11 with risk of Parkinson’s disease
Publisher: Springer Science and Business Media LLC
Date: 06-03-2020
DOI: 10.1038/S41467-020-15065-7
Abstract: An improved understanding of etiological mechanisms in Parkinson’s disease (PD) is urgently needed because the number of affected in iduals is projected to increase rapidly as populations age. We present results from a blood-based methylome-wide association study of PD involving meta-analysis of 229 K CpG probes in 1,132 cases and 999 controls from two independent cohorts. We identify two previously unreported epigenome-wide significant associations with PD, including cg06690548 on chromosome 4. We demonstrate that cg06690548 hypermethylation in PD is associated with down-regulation of the SLC7A11 gene and show this is consistent with an environmental exposure, as opposed to medications or genetic factors with effects on DNA methylation or gene expression. These findings are notable because SLC7A11 codes for a cysteine-glutamate anti-porter regulating levels of the antioxidant glutathione, and it is a known target of the environmental neurotoxin β-methylamino-L-alanine (BMAA). Our study identifies the SLC7A11 gene as a plausible biological target in PD.
Wild-type and mutant (G2019S) leucine-rich repeat kinase 2 (LRRK2) associate with subunits of the translocase of outer mitochondrial membrane (TOM) complex
Publisher: Elsevier BV
Date: 02-2019
DOI: 10.1016/J.YEXCR.2018.12.022
Abstract: Leucine-rich repeat kinase 2 (LRRK2) is important in various cellular processes including mitochondrial homeostasis and mutations in this gene lead to Parkinson's disease (PD). However, the full spectrum of LRRK2's functions remain to be elucidated. The translocase of outer mitochondrial membrane (TOM) complex is essential for the import of almost all nuclear-encoded mitochondrial proteins and is fundamental for cellular survival. Using co-immunoprecipitation, super-resolution structured illumination microscopy (SR-SIM), and 3D virtual reality (VR) assisted co-localization analysis techniques we show that wild-type and mutant (G2019S) LRRK2 associate and co-localize with subunits of the TOM complex, either under basal (dimethyl sulfoxide, DMSO) or stress-induced (carbonyl cyanide m-chlorophenyl hydrazine, CCCP) conditions. Interestingly, LRRK2 interacted with TOM40 under both DMSO and CCCP conditions, and when the PD causing mutation, G2019S was introduced, the association was not altered. Moreover, overexpression of G2019S LRRK2 resulted in the formation of large, perinuclear aggregates that co-localized with the TOM complex. Taken together, this is the first study to show that both WT and mutant LRRK2 associate with the TOM complex subunits. These findings provide additional evidence for LRRK2's role in mitochondrial function which has important implications for its role in PD pathogenesis.
NRF2 Activation Restores Disease Related Metabolic Deficiencies in Olfactory Neurosphere-Derived Cells from Patients with Sporadic Parkinson's Disease
Publisher: Public Library of Science (PLoS)
Date: 07-2011
Independent and joint effects of the MAPT and SNCA genes in Parkinson disease
Publisher: Wiley
Date: 09-03-2011
DOI: 10.1002/ANA.22321
Evaluation of the interaction between LRRK2 and PARK16 loci in determining risk of Parkinson's disease: analysis of a large multicenter study
Publisher: Elsevier BV
Date: 2017
The parkin gene S/N167 polymorphism in Australian Parkinson's disease patients and controls
Publisher: Elsevier BV
Date: 04-2001
DOI: 10.1016/S1353-8020(00)00018-3
Abstract: This study determined the frequencies of a G-to-A transition (S/N167) polymorphism in exon 4 of the parkin gene in Australian Parkinson's disease patients and control subjects. The genotype of each subject was determined using the polymerase chain reaction and restriction-fragment-length-polymorphism analysis. Overall, the A allele was significantly less common in the Parkinson's disease group (1.7%) compared with the control group (3.8%, OR=0.43, 95% CI=0.19-1.00, P<0.05), although the frequency in the young onset Parkinson's disease group (6.6%) was not significantly different to controls. The A allele is less common in Australian Caucasian subjects compared to Japanese Parkinson's disease patients and appears to be under-represented in older-onset Parkinson's disease.
Establishing historical sample data is essential for identification of unaccounted Australian soldiers from WWI, WWII, and the Korean War
Publisher: Informa UK Limited
Date: 10-06-2020
Tau haplotypes regulate transcription and are associated with Parkinson's disease.
Publisher: Wiley
Date: 23-01-2004
DOI: 10.1002/ANA.10826
Abstract: A primary haplotype (H1) of the microtubule-associated protein Tau (MAPT) gene is associated with Parkinson's disease (PD). However, the mechanism for disease susceptibility remains unknown. We examined the promoter region of MAPT and identified single nucleotide polymorphisms and insertions of 1 to 11 nucleotides. These polymorphisms corresponded to the previously characterized haplotypes, H1 and H2, as well as a novel variant of the H1 haplotype, H1'. As observed in other studies, we demonstrated a significant association with the H1/H1 promoter genotype and PD in a cohort of 206 idiopathic late-onset cases. This is in contrast with a panel of 13 early-onset PD patients, for whom we did not detect any mutations in MAPT. By examining single nucleotide polymorphisms in adjacent genes, we showed that linkage disequilibrium does not extend beyond the MAPT haplotype to neighboring genes. To define the mechanism of disease susceptibility, we examined the transcriptional activity of the promoter haplotypes using a luciferase reporter assay. We demonstrated in two human cell lines, SK-N-MC and 293, that the H1 haplotype was more efficient at driving gene expression than the H2 haplotype. Our data suggest that an increase in expression of the MAPT gene is a susceptibility factor in idiopathic PD.
Late‐onset presentation of pyruvate dehydrogenase deficiency
Publisher: Wiley
Date: 03-2004
DOI: 10.1002/MDS.20063
Abstract: Two brothers presented in their mid-forties with movement disorders including atypical parkinsonism, choreiform movements, stereotypies, ataxia and dysarthria. Both brothers showed putaminal lucencies on imaging and, in the proband, a deficiency of the pyruvate dehydrogenase complex (PDHC) was found on skin fibroblast assay.
The protective effect of LRRK2 p.R1398H on risk of Parkinson's disease is independent of MAPT and SNCA variants
Publisher: Elsevier BV
Date: 2014
RELIABILITY OF SELF-REPORTED ENVIRONMENTAL EXPOSURE DATA IN AN EPIDEMIOLOGICAL STUDY OF PARKINSONʼS DISEASE
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 09-2003
Characteristics and Treatment of Anxiety Disorders in Parkinson's Disease
Publisher: Wiley
Date: 06-04-2015
DOI: 10.1002/MDC3.12157
Abstract: Background: Anxiety disorders are common in Parkinson's disease ( PD ) and are undertreated. The current study investigates demographic and PD‐ specific factors associated with Diagnostic and Statistical Manual ( DSM ‐ IV ) anxiety disorders and subsyndromal anxiety in PD . It also examines the use of pharmacological and nonpharmacological treatments for anxiety in PD . Methods: Ninety nondemented PD patients completed a semistructured interview. Logistic regression models were constructed examining associations between several demographic, disease‐specific, and treatment factors, as well as both current syndromal, DSM ‐ IV anxiety disorders, and subsyndromal anxiety. Results: Associations were found between current DSM ‐ IV anxiety disorder, as well as female gender, younger age, more severe stages of PD , and poor activities of daily living. Subsyndromal anxiety was related to a younger onset age of PD . Relationships were also found between both anxiety groups and more complications of PD therapy, as well as higher depression scores. There were no associations between anxiety and levodopa equivalent daily dosage, motor disability, and cognition. In our s le, 57% of patients with current DSM ‐ IV anxiety disorders or subsyndromal anxiety were not currently treated with pharmacotherapy. Of those who currently received such treatment, 83% still experienced current anxiety disorders. Results suggest that anxiety is poorly recognized and treated in PD . Conclusions: Clinical trials investigating the efficacy of pharmacotherapy, tailored psychotherapy, and combination therapy primarily focusing on anxiety are much needed, with the aim of establishing novel targeted treatment protocols for the management of subtypes of anxiety disorders in PD .
NMR Fingerprints of the Drug-like Natural-Product Space Identify Iotrochotazine A: A Chemical Probe to Study Parkinson's Disease
Publisher: Wiley
Date: 15-04-2014
Oxidative Stress in Parkinson's Disease; Parallels Between Current Animal Models, Human Studies and Cells
Publisher: InTech
Date: 25-04-2012
DOI: 10.5772/33459
Corrigendum
Publisher: Oxford University Press (OUP)
Date: 22-03-2017
DOI: 10.1093/BRAIN/AWX055
Meeting the Challenge: Using Cytological Profiling to Discover Chemical Probes from Traditional Chinese Medicines against Parkinson's Disease
Publisher: American Chemical Society (ACS)
Date: 26-10-2016
DOI: 10.1021/ACSCHEMNEURO.6B00245
Abstract: Parkinson's disease (PD) is an incurable neurodegenerative disorder with a high prevalence rate worldwide. The fact that there are currently no proven disease-modifying treatments for PD underscores the urgency for a more comprehensive understanding of the underlying disease mechanism. Chemical probes have been proven to be powerful tools for studying biological processes. Traditional Chinese medicine (TCM) contains a huge reservoir of bioactive small molecules as potential chemical probes that may hold the key to unlocking the mystery of PD biology. The TCM-sourced chemical approach to PD biology can be advanced through the use of an emerging cytological profiling (CP) technique that allows unbiased characterization of small molecules and their cellular responses. This comprehensive technique, applied to chemical probe identification from TCM and used for studying the molecular mechanisms underlying PD, may inform future therapeutic target selection and provide a new perspective to PD drug discovery.
O-GlcNAcylation of truncated NAC segment alters peptide-dependent effects on α-synuclein aggregation
Publisher: Elsevier BV
Date: 2020
DOI: 10.1016/J.BIOORG.2019.103389
Abstract: Numerous post-translational modifications (PTMs) of the Parkinson's disease (PD) associated α-synuclein (α-syn) protein have been recognised to play critical roles in disease aetiology. Indeed, dysregulated phosphorylation and proteolysis are thought to modulate α-syn aggregation and disease progression. Among the PTMs, enzymatic glycosylation with N-acetylglucosamine (GlcNAc) onto the protein's hydroxylated amino acid residues is reported to deliver protective effects against its pathogenic processing. This modification has been reported to alter its pathogenic self-assembly. As such, manipulation of the protein's O-GlcNAcylation status has been proposed to offer a PD therapeutic route. However, targeting upstream cellular processes can lead to mechanism-based toxicity as the enzymes governing O-GlcNAc cycling modify thousands of acceptor substrates. Small glycopeptides that couple the protective effects of O-GlcNAc with the selectivity of recognition sequences may prove useful tools to modulate protein aggregation. Here we discuss efforts to probe the effects of various O-GlcNAc modified peptides on wild-type α-synuclein aggregation.
Mitochondrial DNA Haplogroups J and K are not Protective for Parkinson's Disease in the Australian Community
Publisher: Wiley
Date: 11-12-2009
DOI: 10.1002/MDS.22389
Abstract: MtDNA haplogroups J and K have been associated with a decreased risk of developing Parkinson's disease (PD). To confirm this finding, we compared the distribution of mtDNA haplogroups J and K in a large s le of Australian patients with PD (n = 890) to population-based controls (n = 3,491). We assigned subjects to haplogroups J or K using standard PCR/RFLP techniques. Of the 890 subjects with PD, 10.6% were haplogroup J (95% CI 8.6-12.8, n = 94) and 7.1% were haplogroup K (95% CI 5.5-8.9, n = 63). In our controls, 10.2% belonged to haplogroup J (95% CI 9.2-11.2, n = 356), and 7.8% were in haplogroup K (95% CI 6.9-8.7, n = 272). There was no significant difference in the prevalence of mtDNA haplogroup J or K in PD patients compared to population-based controls. Our findings indicate that mtDNA haplogroups J and K are not associated with a lower risk of PD.
Dexamethasone Inhibits Copper-Induced Alpha-Synuclein Aggregation by a Metallothionein-Dependent Mechanism
Publisher: Springer Science and Business Media LLC
Date: 24-10-2017
DOI: 10.1007/S12640-017-9825-7
Abstract: Intracellular aggregates of α-synuclein are the pathological hallmark of Parkinson's disease (PD) and dementia with Lewy bodies (DLB), being linked to neurotoxicity. Multiple triggers of α-synuclein aggregation have been implicated, including raised copper. The potential protective role of the endogenous copper-/zinc-binding proteins, metallothioneins (MT), has been explored in relation to copper-induced α-synuclein aggregation. Up-regulated endogenous expression of MT was induced in SHSY-5Y cells by the synthetic glucocorticoid analogue, dexamethasone. After treatment to induce endogenous MT expression, immunofluorescence confocal microscopy was used to quantify protein aggregates in cells with/without copper treatment. MT induction resulted in significant (p < 0.01), dose-dependent up-regulation of MT expression and significant reduction in Cu-dependent α-synuclein intracellular aggregates (p < 0.01) that could be suppressed by MT-specific siRNA. Ubiquitous (MT-2) and brain-specific (MT-3) isoforms were investigated by transient transfection of the GFP-fusion proteins, observing equivalent α-synuclein aggregate suppression by each. These studies indicate MT induction could have potential in PD/DLB neuroprotective therapy by suppressing α-synuclein aggregation.
Hepatic Disposition and Metabolite Kinetics of a Homologous Series of Diflunisal Esters
Publisher: American Geophysical Union (AGU)
Date: 08-1998
DOI: 10.1021/JS970485Y
Probabilistic subgroup identification using Bayesian finite mixture modelling: A case study in Parkinson's disease phenotype identification
Publisher: SAGE Publications
Date: 16-12-2012
Abstract: This article explores the use of probabilistic classification, namely finite mixture modelling, for identification of complex disease phenotypes, given cross-sectional data. In particular, if focuses on posterior probabilities of subgroup membership, a standard output of finite mixture modelling, and how the quantification of uncertainty in these probabilities can lead to more detailed analyses. Using a Bayesian approach, we describe two practical uses of this uncertainty: (i) as a means of describing a person's membership to a single or multiple latent subgroups and (ii) as a means of describing identified subgroups by patient-centred covariates not included in model estimation. These proposed uses are demonstrated on a case study in Parkinson's disease (PD), where latent subgroups are identified using multiple symptoms from the Unified Parkinson's Disease Rating Scale (UPDRS).
ER-phagy in neurodegeneration
Publisher: Wiley
Date: 19-06-2023
DOI: 10.1002/JNR.25225
Abstract: There are many cellular mechanisms implicated in the initiation and progression of neurodegenerative disorders. However, age and the accumulation of unwanted cellular products are a common theme underlying many neurodegenerative diseases including Alzheimer's disease, Parkinson's disease, and Niemann–Pick type C. Autophagy has been studied extensively in these diseases and various genetic risk factors have implicated disruption in autophagy homoeostasis as a major pathogenic mechanism. Autophagy is essential in the maintenance of neuronal homeostasis, as their postmitotic nature makes them particularly susceptible to the damage caused by accumulation of defective or misfolded proteins, disease‐prone aggregates, and damaged organelles. Recently, autophagy of the endoplasmic reticulum (ER‐phagy) has been identified as a novel cellular mechanism for regulating ER morphology and response to cellular stress. As neurodegenerative diseases are generally precipitated by cellular stressors such as protein accumulation and environmental toxin exposure the role of ER‐phagy has begun to be investigated. In this review we discuss the current research in ER‐phagy and its involvement in neurodegenerative diseases.
Metabolite mean transit times in the liver as predicted by various models of hepatic elimination.
Publisher: Springer Science and Business Media LLC
Date: 1997
Abstract: Predicted area under curve (AUC), mean transit time (MTT) and normalized variance (CV2) data have been compared for parent compound and generated metabolite following an impulse input into the liver. Models studied were the well-stirred (tank) model, tube model, a distributed tube model, dispersion model (Danckwerts and mixed boundary conditions) and tanks-in-series model. It is well known that discrimination between models for a parent solute is greatest when the parent solute is highly extracted by the liver. With the metabolite, greatest model differences for MTT and CV2 occur when parent solute is poorly extracted. In all cases the predictions of the distributed tube, dispersion, and tanks-in-series models are between the predictions of the tank and tube models. The dispersion model with mixed boundary conditions yields identical predictions to those for the distributed tube model (assuming an inverse gaussian distribution of tube transit times). The dispersion model with Danckwerts boundary conditions and the tanks-in series models give similar predictions to the dispersion (mixed boundary conditions) and the distributed tube. The normalized variance for parent compound is dependent upon hepatocyte permeability only within a distinct range of permeability values. This range is similar for each model but the order of magnitude predicted for normalized variance is model dependent. Only for a one-compartment system is the MTT for generated metabolite equal to the sum of MTTs for the parent compound and preformed metabolite administered as parent.
How Well Do Caregivers Detect Depression and Anxiety in Patients With Parkinson Disease?
Publisher: SAGE Publications
Date: 02-08-2018
Abstract: Depression and anxiety are prevalent in Parkinson disease (PD) yet underrecognized in clinical practice. Caregiver reports are frequently utilized to aid in the assessment of neuropsychiatric symptoms but little is known about caregivers’ ability to recognize them in patients with PD. This study sought to examine the accuracy of caregiver reports. Eighty patient–caregiver dyads were involved. Accuracy of caregiver recognition was assessed by examining the level of agreement between caregiver ratings on the Neuropsychiatric Inventory and patients’ diagnosis of depression and anxiety on the Mini-International Neuropsychiatric Interview (MINI)-Plus. The agreement between caregiver report and MINI-Plus diagnosis was low for both depression (6.3%) and anxiety (17.5%). The presence of depression was overreported, while anxiety was largely underestimated by caregivers. Caregiver distress significantly predicted inaccurate caregiver identification of depression ( R 2 = .51, P .001) and anxiety ( R 2 = .08, P .05). Results indicate that caregivers may be poor at recognizing depression and anxiety in patients with PD. Utilization of caregiver report should take into account potential biases that affect caregiver judgment.
Haplotype analysis of the PARK 11 gene, GIGYF2, in sporadic Parkinson's disease
Publisher: Wiley
Date: 15-02-2009
DOI: 10.1002/MDS.22427
Abstract: Familial Parkinsonism (PARK) genes are strong candidates for conferring susceptibility to common forms of PD. However, most studies to date have provided little evidence that their common variants substantially influence disease risk. Recently, mutations were described in the gene, GIGYF2 (TNRC15), located at the PARK11 locus (2q37.1). Here, we use a haplotype tagging approach to examine common variation in the GIGYF2 gene and PD risk. PD cases (n = 568) and age and gender-matched control subjects (n = 568) were recruited from three specialist movement disorder clinics in Brisbane (Australia) and the Australian electoral roll. Twelve tagging SNPs were assessed in all subjects and haplotype and genotype associations were explored. Overall our findings suggest that common genetic variants of GIGYF2 do not significantly affect sporadic PD risk in Australian Caucasians.
Polygenic Resilience Modulates the Penetrance of Parkinson Disease Genetic Risk Factors
Publisher: Wiley
Date: 24-06-2022
DOI: 10.1002/ANA.26416
Abstract: The aim of the current study is to understand why some in iduals avoid developing Parkinson disease (PD) despite being at relatively high genetic risk, using the largest datasets of in idual‐level genetic data available. We calculated polygenic risk score to identify controls and matched PD cases with the highest burden of genetic risk for PD in the discovery cohort (International Parkinson's Disease Genomics Consortium, 7,204 PD cases and 9,412 controls) and validation cohorts (Comprehensive Unbiased Risk Factor Assessment for Genetics and Environment in Parkinson's Disease, 8,968 cases and 7,598 controls UK Biobank, 2,639 PD cases and 14,301 controls Accelerating Medicines Partnership–Parkinson's Disease Initiative, 2,248 cases and 2,817 controls). A genome‐wide association study meta‐analysis was performed on these in iduals to understand genetic variation associated with resistance to disease. We further constructed a polygenic resilience score, and performed multimarker analysis of genomic annotation (MAGMA) gene‐based analyses and functional enrichment analyses. A higher polygenic resilience score was associated with a lower risk for PD (β = −0.054, standard error [SE] = 0.022, p = 0.013). Although no single locus reached genome‐wide significance, MAGMA gene‐based analyses nominated TBCA as a putative gene. Furthermore, we estimated the narrow‐sense heritability associated with resilience to PD ( h 2 = 0.081, SE = 0.035, p = 0.0003). Subsequent functional enrichment analysis highlighted histone methylation as a potential pathway harboring resilience alleles that could mitigate the effects of PD risk loci. The present study represents a novel and comprehensive assessment of heritable genetic variation contributing to PD resistance. We show that a genetic resilience score can modify the penetrance of PD genetic risk factors and therefore protect in iduals carrying a high‐risk genetic burden from developing PD. ANN NEUROL 2022 :270–278
New evidence for, and challenges in, linking small CGG repeat expansion FMR1 alleles with Parkinson's disease
Publisher: Wiley
Date: 25-12-2012
DOI: 10.1111/CGE.12070
Abstract: We recently reported a significant increase in the frequency of carriers of grey zone (GZ) alleles of FMR1 gene in Australian males with Parkinson's disease (PD) from Victoria and Tasmania. Here, we report data comparing an independent s le of 817 PD patients from Queensland to 1078 consecutive Australian male newborns from Victoria. We confirmed the earlier finding by observing a significant excess of GZ alleles in PD (4.8%) compared to controls (1.5%). Although both studies provided evidence in support of an association between GZ-carrier status and increased risk for parkinsonism, the existing evidence in the literature from screening studies remains equivocal and we discuss the need for alternative approaches to resolve the issue.
Differential patterns of internally generated responses in parkinsonian disorders
Publisher: Elsevier BV
Date: 09-2020
Identification of genetic modifiers of age-at-onset for familial Parkinson’s disease
Publisher: Oxford University Press (OUP)
Date: 11-07-2016
DOI: 10.1093/HMG/DDW206
Kororamide B, a brominated alkaloid from the bryozoan Amathia tortuosa and its effects on Parkinson's disease cells
Publisher: Elsevier BV
Date: 10-2015
DNA methylation of the MAPT gene in Parkinson's disease cohorts and modulation by vitamin E In Vitro
Publisher: Wiley
Date: 27-12-2014
DOI: 10.1002/MDS.25784
A door-to-door survey to estimate the prevalence of Parkinsonism in Pakistan
Publisher: Informa UK Limited
Date: 06-2016
DOI: 10.2147/NDT.S86329
Moving beyond neurons: the role of cell type-specific gene regulation in Parkinson’s disease heritability
Publisher: Springer Science and Business Media LLC
Date: 17-04-2019
DOI: 10.1038/S41531-019-0076-6
Abstract: Parkinson’s disease (PD), with its characteristic loss of nigrostriatal dopaminergic neurons and deposition of α-synuclein in neurons, is often considered a neuronal disorder. However, in recent years substantial evidence has emerged to implicate glial cell types, such as astrocytes and microglia. In this study, we used stratified LD score regression and expression-weighted cell-type enrichment together with several brain-related and cell-type-specific genomic annotations to connect human genomic PD findings to specific brain cell types. We found that PD heritability attributable to common variation does not enrich in global and regional brain annotations or brain-related cell-type-specific annotations. Likewise, we found no enrichment of PD susceptibility genes in brain-related cell types. In contrast, we demonstrated a significant enrichment of PD heritability in a curated lysosomal gene set highly expressed in astrocytic, microglial, and oligodendrocyte subtypes, and in LoF-intolerant genes, which were found highly expressed in almost all tested cellular subtypes. Our results suggest that PD risk loci do not lie in specific cell types or in idual brain regions, but rather in global cellular processes detectable across several cell types.
Comparison of Environmental and Genetic Factors for Parkinson’s Disease between Chinese and Caucasians
Publisher: S. Karger AG
Date: 2004
DOI: 10.1159/000073970
Abstract: This review paper compares the differences in prevalence, and environmental and genetic risk factors for Parkinson’s disease between Chinese and Caucasian subjects. Comparison of age-specific prevalence between Chinese people and Caucasians suggests that the prevalence is lower in the Chinese (at least in the past), although the prevalence rate in China appears to be rising. Distinctions in environmental risk factors and genetic factors are discussed. The difference in prevalence may be due to distinctions in environmental and genetic risk factors as well as the complex interaction between these environmental and genetic factors, although discrepancies in methodology for prevalence surveys can also be an explanation.
Hesperine, a new imidazole alkaloid and α-synuclein binding activity of 1-methyl-1,2,7,8-tetrahydro-2,8-dioxoadenosine from the marine sponge Clathria (Thalysias) cf. hesperia
Publisher: Elsevier BV
Date: 2022
Mitochondrial Modulators: The Defender
Publisher: MDPI AG
Date: 24-01-2023
DOI: 10.3390/BIOM13020226
Abstract: Mitochondria are widely considered the “power hub” of the cell because of their pivotal roles in energy metabolism and oxidative phosphorylation. However, beyond the production of ATP, which is the major source of chemical energy supply in eukaryotes, mitochondria are also central to calcium homeostasis, reactive oxygen species (ROS) balance, and cell apoptosis. The mitochondria also perform crucial multifaceted roles in biosynthetic pathways, serving as an important source of building blocks for the biosynthesis of fatty acid, cholesterol, amino acid, glucose, and heme. Since mitochondria play multiple vital roles in the cell, it is not surprising that disruption of mitochondrial function has been linked to a myriad of diseases, including neurodegenerative diseases, cancer, and metabolic disorders. In this review, we discuss the key physiological and pathological functions of mitochondria and present bioactive compounds with protective effects on the mitochondria and their mechanisms of action. We highlight promising compounds and existing difficulties limiting the therapeutic use of these compounds and potential solutions. We also provide insights and perspectives into future research windows on mitochondrial modulators.
Test-retest repeatability of self-reported environmental exposures in Parkinson's disease cases and healthy controls
Publisher: Elsevier BV
Date: 08-2005
DOI: 10.1016/J.PARKRELDIS.2005.04.002
Abstract: There is substantial disagreement among published epidemiological studies regarding environmental risk factors for Parkinson's disease (PD). Differences in the quality of measurement of environmental exposures may contribute to this variation. The current study examined the test-retest repeatability of self-report data on risk factors for PD obtained from a series of 32 PD cases recruited from neurology clinics and 29 healthy sex-, age- and residential suburb-matched controls. Exposure data were collected in face-to-face interviews using a structured questionnaire derived from previous epidemiological studies. High repeatability was demonstrated for 'lifestyle' exposures, such as smoking and coffee/tea consumption (kappas 0.70-1.00). Environmental exposures that involved some action by the person, such as pesticide application and use of solvents and metals, also showed high repeatability (kappas>0.78). Lower repeatability was seen for rural residency and bore water consumption (kappa 0.39-0.74). In general, we found that case and control participants provided similar rates of incongruent and missing responses for categorical and continuous occupational, domestic, lifestyle and medical exposures.
Passive smoking and Parkinson disease
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 10-07-2006
Disease-specific, neurosphere-derived cells as models for brain disorders
Publisher: The Company of Biologists
Date: 28-10-2010
DOI: 10.1242/DMM.005447
Abstract: There is a pressing need for patient-derived cell models of brain diseases that are relevant and robust enough to produce the large quantities of cells required for molecular and functional analyses. We describe here a new cell model based on patient-derived cells from the human olfactory mucosa, the organ of smell, which regenerates throughout life from neural stem cells. Olfactory mucosa biopsies were obtained from healthy controls and patients with either schizophrenia, a neurodevelopmental psychiatric disorder, or Parkinson’s disease, a neurodegenerative disease. Biopsies were dissociated and grown as neurospheres in defined medium. Neurosphere-derived cell lines were grown in serum-containing medium as adherent monolayers and stored frozen. By comparing 42 patient and control cell lines we demonstrated significant disease-specific alterations in gene expression, protein expression and cell function, including dysregulated neurodevelopmental pathways in schizophrenia and dysregulated mitochondrial function, oxidative stress and xenobiotic metabolism in Parkinson’s disease. The study has identified new candidate genes and cell pathways for future investigation. Fibroblasts from schizophrenia patients did not show these differences. Olfactory neurosphere-derived cells have many advantages over embryonic stem cells and induced pluripotent stem cells as models for brain diseases. They do not require genetic reprogramming and they can be obtained from adults with complex genetic diseases. They will be useful for understanding disease aetiology, for diagnostics and for drug discovery.
Parkinson's disease, pesticides, and glutathione transferase polymorphisms
Publisher: Elsevier BV
Date: 10-1998
DOI: 10.1016/S0140-6736(98)03453-9
Abstract: Parkinson's disease is thought to be secondary to the presence of neurotoxins, and pesticides have been implicated as possible causative agents. Glutathione transferases (GST) metabolise xenobiotics, including pesticides. Therefore, we investigated the role of GST polymorphisms in the pathogenesis of idiopathic Parkinson's disease. We genotyped by PCR polymorphisms in four GST classes (GSTM1, GSTT1, GSTP1, and GSTZ1) in 95 Parkinson's disease patients and 95 controls. We asked all patients for information about pesticide exposure. The distribution of the GSTP1 genotypes differed significantly between patients and controls who had been exposed to pesticides (controls vs patients: AA 14 [54%] of 26 vs seven [18%] of 39 AB 11 [42%] of 26 vs 22 [56%] of 39 BB 1 [4%] of 26 vs six [15%] of 39 AC 0 vs four [10%] of 39, p=0.009). No association was found with any of the other GST polymorphisms. Pesticide exposure and a positive family history were risk factors for Parkinson's disease. GSTP1-1, which is expressed in the blood-brain barrier, may influence response to neurotoxins and explain the susceptibility of some people to the parkinsonism-inducing effects of pesticides.
Strong Predictive Algorithm of Pathogenesis-Based Biomarkers Improves Parkinson's Disease Diagnosis
Publisher: Springer Science and Business Media LLC
Date: 07-01-2022
DOI: 10.1007/S12035-021-02604-6
Abstract: Easily accessible and accurate biomarkers can aid Parkinson's disease diagnosis. We investigated whether combining plasma levels of α-synuclein, anti-α-synuclein, and/or their ratios to amyloid beta-40 correlated with clinical diagnosis. The inclusion of amyloid beta-40 (Aβ40) is novel. Plasma levels of biomarkers were quantified with ELISA. Using receiver operating characteristic (ROC) curve analysis, levels of α-synuclein, anti-α-synuclein, and their ratios with Aβ40 were analyzed in an initial training set of cases and controls. Promising biomarkers were then used to build a diagnostic algorithm. Verification of the results of biomarkers and the algorithm was performed in an independent set. The training set consisted of 50 cases (age 65.2±9.3, range 44-83, female:male=21:29) with 50 age- and gender-matched controls (67.1±10.0, range 45-96 years female:male=21:29). ROC curve analysis yielded the following area under the curve results: anti-α-synuclein=0.835, α-synuclein=0.738, anti-α-synuclein/Aβ40=0.737, and α-synuclein/Aβ40=0.663. A 2-step diagnostic algorithm was built: either α-synuclein or anti-α-synuclein was ≥2 times the means of controls (step-1), resulting in 74% sensitivity and adding α-synuclein/Aβ40 or anti-α-synuclein/Aβ40 (step-2) yielded better sensitivity (82%) while using step-2 alone yielded good specificity in controls (98%). The results were verified in an independent s le of 46 cases and 126 controls, with sensitivity reaching 91.3% and specificity 90.5%. The algorithm was equally sensitive in Parkinson's disease of ≤5-year duration with 92.6% correctly identified in the training set and 90% in the verification set. With two independent s les totaling 272 subjects, our study showed that combination of biomarkers of α-synuclein, anti-α-synuclein, and their ratios to Aβ40 showed promising sensitivity and specificity.
Collaborative Analysis of α-Synuclein Gene Promoter Variability and Parkinson Disease
Publisher: American Medical Association (AMA)
Date: 09-08-2006
Abstract: Identification and replication of susceptibility genes for Parkinson disease at the population level have been h ered by small studies with potential biases. Alpha-synuclein (SNCA) has been one of the most promising susceptibility genes, but large-scale studies have been lacking. To determine whether allele-length variability in the dinucleotide repeat sequence (REP1) of the SNCA gene promoter is associated with Parkinson disease susceptibility, whether SNCA promoter haplotypes are associated with Parkinson disease, and whether REP1 variability modifies age at onset. We performed a collaborative analysis of in idual-level data on SNCA REP1 and flanking markers in patients with Parkinson disease and controls. Study site recruitment, data collection, and analyses were performed between April 5, 2004, and December 31, 2005. Eighteen participating sites of a global genetics consortium provided clinical data. Genotyping was performed for SNCA REP1, -770, and -116 markers at in idual sites however, each site also provided 20 DNA s les for regenotyping centrally. Measures included estimations of Hardy-Weinberg equilibrium in controls a test of heterogeneity analyses for association of single variants or haplotypes and survival analyses for age at onset. Of the 18 sites, 11 met stringent criteria for concordance with Hardy-Weinberg equilibrium and low genotyping error rate. These 11 sites provided complete data for 2692 cases and 2652 controls. There was no heterogeneity across studies (P>.60). The SNCA REP1 alleles differed in frequency for cases and controls (P<.001). Genotypes defined by the 263 base-pair allele were associated with Parkinson disease (odds ratio, 1.43 95% confidence interval, 1.22-1.69 P<.001 for trend). Multilocus haplotypes differed in frequency for cases and controls (global score statistic, P<.001). Two-loci haplotypes were associated with Parkinson disease only when they included REP1 as one of the loci. However, genotypes defined by REP1 alleles did not modify age at onset (P = .55). This large-scale collaborative analysis demonstrates that SNCA REP1 allele-length variability is associated with an increased risk of Parkinson disease.
Advances in the development of imaging probes and aggregation inhibitors for alpha-synuclein
Publisher: Springer Science and Business Media LLC
Date: 04-10-2020
USE OF A SOLUTE CONTAINER INTERACTION TO DETERMINE PROTEIN-BINDING - APPLICATION TO LONG-CHAIN FATTY-ACIDS
Publisher: Elsevier BV
Date: 10-1993
Glutathione transferase polymorphism and Parkinson's disease
Publisher: Elsevier BV
Date: 1999
Serotonin and dopamine transporter genes do not influence depression in Parkinson's disease
Publisher: Wiley
Date: 15-01-2009
DOI: 10.1002/MDS.22134
Abstract: Altered levels of the neurotransmitters dopamine and serotonin are observed in both Parkinson's disease (PD) and depression. Therefore, the neurotransmitter transporter genes, SLC6A3 (dopamine) and SLC6A4 (serotonin) are candidates for depression in PD. We genotyped 24 tagging SNPs together with VNTRs and the SLC6A4 LPR polymorphism in 190 PD patients categorised according to lifetime history of depression. Log-additive, dominant and recessive statistical models were constructed. No significant genotype or haplotype associations were observed suggesting that common genetic variables around the dopamine and serotonin transporter genes do not play a significant role in the etiology of depression in PD.
The Australian Parkinson’s Genetics Study (APGS) - pilot (N = 1,532)
Publisher: Cold Spring Harbor Laboratory
Date: 07-04-2021
DOI: 10.1101/2021.04.02.21254825
Abstract: Parkinson’s disease (PD) is a neurodegenerative disorder associated with progressive disability. While the precise aetiology is unknown, there is evidence of significant genetic and environmental influences on in idual risk. The Australian Parkinson’s Genetics Study (APGS) seeks to study genetic and patient-reported data from a large cohort of in iduals with PD in Australia to understand the sociodemographic, genetic, and environmental basis of PD susceptibility, symptoms and progression. In the pilot phase reported here, 1,819 participants were recruited through assisted mailouts facilitated by Services Australia based on having three or more prescriptions for anti-PD medications in their Pharmaceutical Benefits Scheme (PBS) records. The average age at the time of the questionnaire was 64 ± 6 years. We collected patient-reported PD information and socio-demographic variables via an online (93% of the cohort) or paper-based (7%) questionnaire. One thousand five hundred thirty-two participants (84.2%) met all inclusion criteria, and 1,499 provided a DNA s le via traditional post. 65% of participants were male, and 92% identified as being of European descent. A previous traumatic brain injury was reported by 16% of participants and was correlated with a younger age of symptom onset. At the time of the questionnaire, constipation (36% of participants), depression (34%), anxiety (17%), melanoma (16%) and diabetes (10%) were the most reported comorbid conditions. We plan to recruit sex- and age-matched unaffected controls, genotype all participants, and collect non-motor symptoms and cognitive function data. Future work will explore the role of genetic and environmental factors in the aetiology of PD susceptibility, onset, symptoms, and progression, including as part of international PD research consortia. We used a time- and cost-effective recruitment method that enabled us to reach out to a random s le of in iduals who have been prescribed medications for Parkinson’s disease across all over Australia to invite them to participate in this study. The identities of letter recipients remained private and confidential and were not shared with the researchers. However, those recipients who were interested and willing to participate were directed to a website where they could sign up and provide informed consent. The source database only captures in iduals who have been prescribed medications to treat Parkinson’s disease in Australia and who are eligible for Medicare. Those without an official diagnosis, not receiving treatment, or not eligible for government subsidies are not included. We collected a wide range of patient-reported variables relevant to disease onset, diagnosis, symptoms, medical comorbidities, lifestyle, and family history in a large cohort of participants. However, some variables might not be as accurate as when measured by a specialist clinician. Given the 9% response rate to our single-letter invitation, there is a substantial risk of self-selection bias. Thus, patient characteristics for this cohort might differ from those of the typical population of in iduals with Parkinson’s disease in Australia.
Meeting the Challenge 2: Identification of Potential Chemical Probes for Parkinson’s Disease from Ligusticum chuanxiong Hort Using Cytological Profiling
Publisher: American Chemical Society (ACS)
Date: 26-08-2022
DOI: 10.1021/ACSCHEMNEURO.1C00820
Abstract: Traditional Chinese medicine (TCM) has been around for thousands of years and is increasingly gaining popularity in the Western world to treat various complex disorders including the incurable neurodegenerative condition, Parkinson's Disease (PD). One of the many directions in recent studies of PD is utilizing the phenotypic assay, or cytological profiling, to evaluate the phenotypic changes of PD-implicated cellular components in patient-derived olfactory neuroepithelial (hONS) cells, upon treating the cells with extracts or pure compounds. To obtain small molecules for studies utilizing PD phenotyping assays,
A functional polymorphism in the parkin gene promoter affects the age of onset of Parkinson's disease
Publisher: Elsevier BV
Date: 03-2007
DOI: 10.1016/J.NEULET.2006.12.051
Abstract: Mutations in the parkin gene are the major cause of autosomal recessive early-onset forms of Parkinson's disease (PD). As reduced parkin expression might also affect the clinical course of idiopathic PD we investigated the effect of a low expressing allele in the parkin promoter region on the age at disease onset (AAO). Patients with PD (n=175) fulfilling standard diagnostic criteria were recruited by experienced neurologists at two movement disorders clinics in Sydney and Brisbane, Australia. DNA was extracted from whole blood and the -258 T/G polymorphism genotyped using PCR/RFLP. AAO effects were analysed using univariate ANOVA, binomial logistic regression modelling and Kaplan-Meier survival analysis. Subjects with the GG genotype (n=10, mean AAO=46.2+/-11.5 (S.D.) years) had a significantly lower mean AAO compared to the common TT genotype (n=104, mean AAO=56.1+/-12.7, p=0.02). There was no difference in mean AAO between the TT and TG in iduals (n=61, mean AAO=55.3+/-11.6). Stratifying the s le by median AAO (55 years) revealed that the GG genotype was over-represented in the early-onset group (n=9, OR=18.6, 95% CI=1.41-245.3, p=0.03). We speculate that reduced expression of normal parkin protein may result in an early manifestation of PD symptoms.
Validity of a self‐rated method to identify a lifetime history of depression in Parkinson's disease
Publisher: Wiley
Date: 15-12-2009
DOI: 10.1002/MDS.22819
Synthesis, identification, characterization, stability, solubility, and protein binding of ester derivatives of salicylic acid and diflunisal
Publisher: Elsevier BV
Date: 07-1997
Phlegmacaritones A and B, a Pair of Serratane-Related Triterpenoid Epimers with an Unprecedented Carbon Skeleton from Phlegmariurus carinatus
Publisher: American Chemical Society (ACS)
Date: 25-02-2021
DOI: 10.1021/ACS.JNATPROD.1C01021
Abstract: A pair of novel serratane-related triterpenoid epimers, phlegmacaritones A (
Perspective: Current Pitfalls in the Search for Future Treatments and Prevention of Parkinson's Disease.
Publisher: Frontiers Media SA
Date: 08-07-2020
Single and dual task gait training in people with Parkinson's Disease: A protocol for a randomised controlled trial
Publisher: Springer Science and Business Media LLC
Date: 27-07-2011
The effect of protein binding on the hepatic first pass of O-acyl salicylate derivatives in the rat
Publisher: Oxford University Press (OUP)
Date: 1998
DOI: 10.1111/J.2042-7158.1998.TB03306.X
Abstract: In this work the in-situ perfused rat liver has been used to examine the effect of changing the protein content of the perfusate on the hepatic extraction of O-acyl esters of salicylic acid. The hepatic availability (F) of these solutes was studied at a flow-rate of 30 mL min−1 with perfusate albumin concentrations of 0, 2, and 4% w/v. The hepatic availability of the esters was shown to decrease with increasing carbon-chain length in the O-acyl group for all the esters the hepatic availability increased with increasing albumin concentration in the perfusate. The dispersion-model-derived efficiency number (RN) of the esters was shown to increase with increasing lipophilicity and decrease with increasing albumin concentration in the perfusate. The unbound fraction (fu) of the esters decreased with lipophilicity. RN/fu for acetylsalicylic acid remained relatively constant as the albumin concentration was increased. However, RN/fu for n-pentanoyl-and n-hexanoylsalicylic acids increased significantly as albumin concentration increased from 0% to 4%. Thus, for the more lipophilic solutes (n-pentanoyl- and n-hexanoylsalicylic acids) the presence of albumin apparently facilitates the uptake of unbound solute relative to acetylsalicylic acid.
Genetic and environmental risk factors and their interactions for Parkinson’s disease in a Chinese population
Publisher: Elsevier BV
Date: 05-2003
DOI: 10.1016/S0967-5868(03)00014-6
Abstract: The interaction between genetic and environmental factors for PD was examined in a Chinese population. It was found that although the intron 2 MAOB (GT)(n) repeat polymorphism was not associated with PD in the population, a relationship might have been masked by the "protective effect" of tea drinking. In in iduals who did not drink tea (<1 cup/day), the possession of short length < or = 178 bp (GT)(n) alleles conferred a borderline significant increased risk for PD (adjusted OR=1.47 C.I.=1.03-2.1). As the extent of tea consumption increased, the association between the < or = 178 bp allele and PD disappeared. This result suggests that the MAOB gene may be associated with PD in Chinese if the putative protective effect of tea drinking is taken into account. The significance of this finding is unclear as the study may be limited because of its marginal significance and limited numbers. However, it does demonstrate the importance of considering putative positive and negative environmental risk factors in any examination of genetic risk factors for PD.
Mitochondrial and Clearance Impairment in p.D620N VPS35 Patient‐Derived Neurons
Publisher: Wiley
Date: 03-11-2020
DOI: 10.1002/MDS.28365
Prevalence of Parkinson’s disease in metropolitan and rural Queensland: A general practice survey
Publisher: Elsevier BV
Date: 04-2006
DOI: 10.1016/J.JOCN.2005.04.015
Abstract: The prevalence of idiopathic Parkinson's disease (IPD) in Australia is unclear. We estimated the prevalence of IPD, and other forms of parkinsonism, through the study of typical caseloads in general practice. A random s le of general practitioners (GPs) throughout Queensland (401 responses from 528 validated practice addresses) was asked to estimate the numbers of patients with IPD and parkinsonism seen in the preceding year. The estimated prevalence of diagnosed IPD in Queensland was 146 per 100,000 (95% CI=136-155). A further 51 per 100,000 in the population were suspected by doctors to have IPD without formal diagnosis, whereas another 51 per 100,000 people may have non-idiopathic parkinsonism. Idiopathic Parkinson's disease was more common in rural than metropolitan areas. Although most GPs were confident in making diagnoses of IPD, the majority had little or no confidence in their ability to treat the disease, especially in its later stages. Support from neurologists was perceived by GPs to be very good in cities, but poor in remote areas.
Disease-specific anxiety symptomatology in Parkinson's disease
Publisher: Cambridge University Press (CUP)
Date: 10-02-2016
DOI: 10.1017/S1041610215002410
Abstract: Symptoms of anxiety relating to Parkinson's disease (PD) occur commonly and include symptomatology associated with motor disability and complications arising from PD medication. However, there have been relatively few attempts to profile such disease-specific anxiety symptoms in PD. Consequently, anxiety in PD is underdiagnosed and undertreated. The present study characterizes PD-related anxiety symptoms to assist with the more accurate assessment and treatment of anxiety in PD. Ninety non-demented PD patients underwent a semi-structured diagnostic assessment targeting anxiety symptoms using relevant sections of the Mini International Neuropsychiatric Interview (MINI-plus). In addition, they were assessed for the presence of 30 PD-related anxiety symptoms derived from the literature, the clinical experience of an expert panel and the PD Anxiety-Motor Complications Questionnaire (PDAMCQ). The onset of anxiety in relation to the diagnosis of PD was determined. Frequent ( %) PD-specific anxiety symptoms included distress, worry, fear, agitation, embarrassment, and social withdrawal due to motor symptoms and PD medication complications, and were experienced more commonly in patients meeting DSM-IV criteria for an anxiety disorder. The onset of common anxiety disorders was observed equally before and after a diagnosis of PD. Patients in a residual group of Anxiety Not Otherwise Specified had an onset of anxiety after a diagnosis of PD. Careful characterization of PD-specific anxiety symptomatology provides a basis for conceptualizing anxiety and assists with the development of a new PD-specific measure to accurately assess anxiety in PD.
A Grand Challenge. 2. Phenotypic Profiling of a Natural Product Library on Parkinson's Patient-Derived Cells
Publisher: American Chemical Society (ACS)
Date: 22-07-2016
DOI: 10.1021/ACS.JNATPROD.6B00258
Abstract: Harnessing the inherent biological relevance of natural products requires a method for the recognition of biological effects that may subsequently lead to the discovery of particular targets. An unbiased multidimensional profiling method was used to examine the activities of natural products on primary cells derived from a Parkinson's disease patient. The biological signature of 482 natural products was examined using multiparametric analysis to investigate known cellular pathways and organelles implicated in Parkinson's disease such as mitochondria, lysosomes, endosomes, apoptosis, and autophagy. By targeting several cell components simultaneously the chance of finding a phenotype was increased. The phenotypes were then clustered using an uncentered correlation. The multidimensional phenotypic screening showed that all natural products, in our screening set, were biologically relevant compounds as determined by an observed phenotypic effect. Multidimensional phenotypic screening can predict the cellular function and subcellular site of activity of new compounds, while the cluster analysis provides correlation with compounds with known mechanisms of action. This study reinforces the value of natural products as biologically relevant compounds.
Investigation of Shared Genetic Risk Factors Between Parkinson's Disease and Cancers
Publisher: Wiley
Date: 14-02-2023
DOI: 10.1002/MDS.29337
Abstract: Epidemiological studies that examined the association between Parkinson's disease (PD) and cancers led to inconsistent results, but they face a number of methodological difficulties. We used results from genome‐wide association studies (GWASs) to study the genetic correlation between PD and different cancers to identify common genetic risk factors. We used in idual data for participants of European ancestry from the Courage‐PD (Comprehensive Unbiased Risk Factor Assessment for Genetics and Environment in Parkinson's Disease PD, N = 16,519) and EPITHYR (differentiated thyroid cancer, N = 3527) consortia and summary statistics of GWASs from iPDGC (International Parkinson Disease Genomics Consortium PD, N = 482,730), Melanoma Meta‐Analysis Consortium (MMAC), Breast Cancer Association Consortium (breast cancer), the Prostate Cancer Association Group to Investigate Cancer Associated Alterations in the Genome (prostate cancer), International Lung Cancer Consortium (lung cancer), and Ovarian Cancer Association Consortium (ovarian cancer) (N comprised between 36,017 and 228,951 for cancer GWASs). We estimated the genetic correlation between PD and cancers using linkage disequilibrium score regression. We studied the association between PD and polymorphisms associated with cancers, and vice versa, using cross‐phenotypes polygenic risk score (PRS) analyses. We confirmed a previously reported positive genetic correlation of PD with melanoma (G corr = 0.16 [0.04 0.28]) and reported an additional significant positive correlation of PD with prostate cancer (G corr = 0.11 [0.03 0.19]). There was a significant inverse association between the PRS for ovarian cancer and PD (odds ratio [OR] = 0.89 [0.84 0.94]). Conversely, the PRS of PD was positively associated with breast cancer (OR = 1.08 [1.06 1.10]) and inversely associated with ovarian cancer (OR = 0.95 [0.91 0.99]). The association between PD and ovarian cancer was mostly driven by rs183211 located in an intron of the NSF gene (17q21.31). We show evidence in favor of a contribution of pleiotropic genes to the association between PD and specific cancers. © 2023 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society. This article has been contributed to by U.S. Government employees and their work is in the public domain in the USA.
CYP450, genetics and Parkinson’s disease: gene × environment interactions hold the key
Publisher: Springer Vienna
Date: 2006
DOI: 10.1007/978-3-211-45295-0_25
Abstract: The ecogenetic theory contends that most cases of Parkinson's disease (PD) result from the actions of environmental factors in genetically susceptible in iduals on a background of normal ageing. This notion is supported by epidemiologic data family history of PD and exposures to environmental toxins such as pesticides increase risk, while cigarette smoking reduces risk. As a result, polymorphic genes that code for metabolic enzymes have been considered as candidates for conferring differential risk for PD. Given their prominence in xenobiotic metabolism, the cytochrome P450 (CYP) genes have come under great scrutiny. The activity of CYP2D6 is largely determined by genetic variability and common sequence variants exist in human populations that lead to poor metaboliser (PM) phenotypes. These have been extensively studied as genetic risk factors for PD with inconsistent results. However, these studies have disregarded interactive effects (e.g. gene x environment interactions) despite the assertions of the ecogenetic theory. Data from our group and others suggest that the CYP2D6 PM genotype interacts with certain environmental factors such as pesticide exposure and cigarette smoking to confer differential risk for PD. Previous failure to consider such interactions might, in part, explain the inconsistencies observed in the CYP2D6 genetic risk-factor literature. Our data illustrate, using CYP2D6 as an exemplar, that it is crucial to consider both genetic and environmental factors, and their interactions, in any examination of risk factors for PD.
Plasma biomarkers inclusive of α-synuclein/amyloid-beta40 ratio strongly correlate with Mini-Mental State Examination score in Parkinson’s disease and predict cognitive impairment
Publisher: Springer Science and Business Media LLC
Date: 25-07-2022
DOI: 10.1007/S00415-022-11287-5
Abstract: Plasma biomarkers for Parkinson’s disease (PD) diagnosis that carry predictive value for cognitive impairment are valuable. We explored the relationship of Mini-Mental State Examination (MMSE) score with plasma biomarkers in PD patients and compared results to vascular dementia (VaD) and normal controls. The predictive accuracy of an in idual biomarker on cognitive impairment was evaluated using area under the receiver operating characteristic curve (AUROC), and multivariate logistic regression was applied to evaluate predictive accuracy of biomarkers on cognitive impairment 178 subjects (41 PD, 31 VaD and 106 normal controls) were included. In multiple linear regression analysis of PD patients, α-synuclein, anti-α-synuclein, α-synuclein/Aβ40 and anti-α-synuclein/Aβ40 were highly predictive of MMSE score in both full model and parsimonious model ( R 2 = 0.838 and 0.835, respectively) compared to non-significant results in VaD group ( R 2 = 0.149) and in normal controls ( R 2 = 0.056). Α-synuclein and anti-α-synuclein/Aβ40 were positively associated with MMSE score, and anti-α-synuclein, α-synuclein/Aβ40 were negatively associated with the MMSE score among PD patients (all P s 0.005). In the AUROC analysis, anti-α-synuclein (AUROC = 0.788) and anti-α-synuclein/Aβ40 (AUROC = 0.749) were significant in idual predictors of cognitive impairment. In multivariate logistic regression, full model of combined biomarkers showed high accuracy in predicting cognitive impairment (AUROC = 0.890 95%CI 0.796–0.984) for PD versus controls, as was parsimonious model (AUROC = 0.866 95%CI 0.764–0.968). In conclusion, simple combination of biomarkers inclusive of α-synuclein/Aβ40 strongly correlates with MMSE score in PD patients versus controls and is highly predictive of cognitive impairment.
Case-only study of interactions between genetic polymorphisms of GSTM1, P1, T1 and Z1 and smoking in Parkinson’s disease
Publisher: Elsevier BV
Date: 08-2004
Editorial: Celebrating the Diversity of Genetic Research to Dissect the Pathogenesis of Parkinson's Disease
Publisher: Frontiers Media SA
Date: 06-04-2021
Related Organisations
Related Funding Activities
Linkage Projects - Grant ID: LP0775106
Start Date: 09-2007
End Date: 09-2010
Amount: $219,108.00
Funder: Australian Research Council
View Funded ActivityLinkage - International - Grant ID: LX0882502
Start Date: 06-2008
End Date: 12-2010
Amount: $75,514.00
Funder: Australian Research Council
View Funded ActivityLinkage Infrastructure, Equipment And Facilities - Grant ID: LE180100200
Start Date: 01-2018
End Date: 12-2019
Amount: $270,427.00
Funder: Australian Research Council
View Funded Activity