ORCID Profile
0000-0002-2374-6329
Current Organisation
University Of Strathclyde
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Publisher: Springer Science and Business Media LLC
Date: 18-09-2011
DOI: 10.1038/NG.940
Publisher: Springer Science and Business Media LLC
Date: 30-07-2008
DOI: 10.1038/NATURE07239
Publisher: Portland Press Ltd.
Date: 22-03-2010
DOI: 10.1042/BST0380445
Abstract: Understanding how cognitive processes including learning, memory, decision making and ideation are encoded by the genome is a key question in biology. Identification of sets of genes underlying human mental disorders is a path towards this objective. Schizophrenia is a common disease with cognitive symptoms, high heritability and complex genetics. We have identified genes involved with schizophrenia by measuring differences in DNA copy number across the entire genome in 91 schizophrenia cases and 92 controls in the Scottish population. Our data reproduce rare and common variants observed in public domain data from & schizophrenia cases, confirming known disease loci as well as identifying novel loci. We found copy number variants in PDE10A (phosphodiesterase 10A), CYFIP1 [cytoplasmic FMR1 (Fragile X mental retardation 1)-interacting protein 1], K+ channel genes KCNE1 and KCNE2, the Down's syndrome critical region 1 gene RCAN1 (regulator of calcineurin 1), cell-recognition protein CHL1 (cell adhesion molecule with homology with L1CAM), the transcription factor SP4 (specificity protein 4) and histone deacetylase HDAC9, among others (see www.genes2cognition.org/SCZ-CNV). Integrating the function of these many genes into a coherent model of schizophrenia and cognition is a major unanswered challenge.
Publisher: Oxford University Press (OUP)
Date: 11-03-2017
Publisher: Springer Science and Business Media LLC
Date: 07-2009
DOI: 10.1038/NATURE08185
Publisher: Springer Science and Business Media LLC
Date: 24-04-2007
Abstract: Several independent linkage studies have identified chromosome 4p15-p16 as a putative region of susceptibility for bipolar disorder (BP), schizophrenia (SCZ) and related phenotypes. Previously, we identified two subregions (B and D) of the 4p15-p16 region that are shared by three of four 4p-linked families examined. Here, we describe a large-scale association analysis of regions B and D (3.8 and 4.5 Mb, respectively). We selected 408 haplotype-tagging single nucleotide polymorphisms (SNPs) on a block-by-block basis from the International HapMap project and tested them in 368 BP, 386 SCZ and 458 control in iduals. Nominal significance thresholds were determined using principal component analysis as implemented in the program SNPSpD. In region B, overlapping SNPs and haplotypes met the region-wide threshold (P<or=0.0005) at the global and in idual haplotype test level and clustered in two regions. In region D, no in idual SNPs were nominally significant, but multiple global and in idual haplotypes were associated with BP and/or SCZ (region-wide threshold, P<or=0.0003). These overlapping haplotypes fell into two regions. Within each of these four clusters, at least one globally significant haplotype withstood permutation testing (P(gp)<or=0.05). Five predicted genes were found within these associated regions, while Known/RefSeq genes, including KIAA0746 and PPARGC1A, mapped nearby. There were also nine other clusters within regions B and D with nominally significant haplotypes, but only at the in idual haplotype level. KIAA0746, PPARGC1A, GPR125, CCKAR and DKFZp761B107 overlapped with these regions. This study has identified significant associations between BP and SCZ within the chromosome 4p linkage region, resulting in candidate regions worthy of further investigation.
Publisher: Cold Spring Harbor Laboratory
Date: 2003
Publisher: Elsevier
Date: 1999
Publisher: Springer Science and Business Media LLC
Date: 20-05-2019
DOI: 10.1007/S12035-019-1638-7
Abstract: The innate immune system and inflammatory response in the brain have critical impacts on the pathogenesis of many neurodegenerative diseases including Alzheimer's disease (AD). In the central nervous system (CNS), the innate immune response is primarily mediated by microglia. However, non-glial cells such as neurons could also partake in inflammatory response independently through inflammasome signalling. The NLR family pyrin domain-containing 1 (NLRP1) inflammasome in the CNS is primarily expressed by pyramidal neurons and oligodendrocytes. NLRP1 is activated in response to amyloid-β (Aβ) aggregates, and its activation subsequently cleaves caspase-1 into its active subunits. The activated caspase-1 proteolytically processes interleukin-1β (IL-1β) and interleukin-18 (IL-18) into maturation whilst co-ordinately triggers caspase-6 which is responsible for apoptosis and axonal degeneration. In addition, caspase-1 activation induces pyroptosis, an inflammatory form of programmed cell death. Studies in murine AD models indicate that the Nlrp1 inflammasome is indeed upregulated in AD and neuronal death is observed leading to cognitive decline. However, the mechanism of NLRP1 inflammasome activation in AD is particularly elusive, given its structural and functional complexities. In this review, we examine the implications of the human NLRP1 inflammasome and its signalling pathways in driving neuroinflammation in AD.
Publisher: Springer Science and Business Media LLC
Date: 11-08-2202
DOI: 10.1038/NG.2711
Location: United Kingdom of Great Britain and Northern Ireland
Location: United Kingdom of Great Britain and Northern Ireland
Location: United Kingdom of Great Britain and Northern Ireland
No related grants have been discovered for Benjamin Pickard.