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Developing Insight Into The Molecular Origins Of Familial And Sporadic Frontotemporal Dementia And Amyotrophic Lateral Sclerosis
Funder
National Health and Medical Research Council
Funding Amount
$6,377,279.00
Summary
There is strong evidence that frontotemporal dementia (FTD) and amyotrophic lateral sclerosis (ALS) represent a spectrum of neurodegenerative disease with common origins. A combined study of FTD/ALS patient cohorts will provide greater power to identify these shared molecular origins. We aim to discover gene variants that cause, predispose, or modify onset and progression of inherited and sporadic FTD/ALS, and validate and study our discoveries in new cell and animal models of these disorders.
New Nanoparticle Strategies For Efficient Delivery And Controlled Release Into The Brain
Funder
National Health and Medical Research Council
Funding Amount
$571,633.00
Summary
A key challenge for treating neurodegenerative diseases is delivery of drugs across the blood–brain barrier (BBB). This project will develop advanced BBB “nanoshuttles” based upon systematic investigation of BBB penetration mechanisms and near-infrared drug controlled release strategy. These delivery systems may facilitate diagnosis of brain diseases and on-demand release of drug cargos to diseased cells in the brain, offering the potential of a brand new localised therapy for brain diseases.
Trace Element Regulation In Neurological Disease: From Molecular Pathogenesis To Translational Impact.
Funder
National Health and Medical Research Council
Funding Amount
$631,370.00
Summary
Neurodegenerative diseases such as dementia and motor neuron disease are a major health burden for Australia and new approaches to treatment are urgently required. Essential trace elements such as copper, zinc and iron show major changes in neurodegneration, however, we do not understand how this drives disease processes. This proposal will develop an innovative 3D ‘brain on a chip’ cell model to probe the role of trace elements in brain pathology and identify exciting new treatments options.
Defining The Function Of Apolipoprotein-D In Alzheimer's Disease
Funder
National Health and Medical Research Council
Funding Amount
$457,231.00
Summary
Alzheimer's disease (AD) prevalence is rising and there is no curative treatment. Neurotoxic amyloid-beta peptide and concomitant lipid oxidation in the brain contribute to the cause of AD. We have identified a new pathway by which a protein called apoD may inhibit lipid oxidation in the AD brain. We will test the impact that changing apoD levels in neurons and in genetically modified mice has on neuron stress and AD-like characteristics. This may reveal new avenues to prevent or treat AD.
Lysosomal Dysfunction As An Inhibitor Of Vitamin B12 Utilisation In Neurodegenerative Diseases
Funder
National Health and Medical Research Council
Funding Amount
$554,901.00
Summary
Vitamin B12 is required for red blood cell formation, DNA synthesis and normal neurological function. B12 deficiency contributes to age-related cognitive decline and Alzheimer’s disease. This research will provide important new information regarding the ageing process and the impact that brain changes associated with ageing and Alzheimer's disease have on B12 metabolism. It will provide important information related to the therapeutic potential of B12.
The research outlined in this application seeks to examine the role of calcium in the pathogenesis of AD. It will examine the hypothesis that the build-up of a protein known as the Abeta causes an increase in levels of calcium in nerve cells of the brain. This increase in calcium may trigger nerve cell damage and dementia. The ultimate aim of the research is to identify new targets for drug development in Alzheimer's disease.
Stimulation Of Neurogenesis By Growth Hormone To Improve Cognition In An Aged Animal Model Of Dementia
Funder
National Health and Medical Research Council
Funding Amount
$550,828.00
Summary
Production of new neurons in the hippocampus of adult animals plays a role in regulating learning and memory, and this production slows continuously with increasing age. Here we explore ways to activate dormant populations of neurogenic precursor cells in the hippocampus to produce new neurons. Since the precursor cells are still present in the hippocampus of an aged animal these studies will provide unequivocal evidence for their importance in reversing age-related cognitive decline and dementi ....Production of new neurons in the hippocampus of adult animals plays a role in regulating learning and memory, and this production slows continuously with increasing age. Here we explore ways to activate dormant populations of neurogenic precursor cells in the hippocampus to produce new neurons. Since the precursor cells are still present in the hippocampus of an aged animal these studies will provide unequivocal evidence for their importance in reversing age-related cognitive decline and dementia.Read moreRead less
Properties Of Dendritic Spines And Their Role In Synaptic Plasticity
Funder
National Health and Medical Research Council
Funding Amount
$336,767.00
Summary
Connections between nerve cells in the brain often occur onto enlarged protrusions called dendritic spines. This proposal will investigate the properties of dendritic spines, and relate differences in spine properties to synaptic plasticity. This information can be used to better understand and treat neurological disorders associated with spine malfunction, as occur in some forms of mental retardation, and may help with understanding the memory loss that occurs during ageing and dementia.
Association Between Sirtuin Single Nucleotide Polymorphisms And Functional Markers Of Brain Health In Ageing
Funder
National Health and Medical Research Council
Funding Amount
$311,860.00
Summary
Sirtuins are histone deacetylases that have been reported to play a pivotal role in energy expenditure, mitochondrial function and pathogenesis of metabolic diseases, including neurodegenerative disorders and Alzheimer’s disease in particular. In this study, we will focus on the genes encoding sirtuin families, and examined the association between single nucleotide polymorphisms within genes encoding sirtuin families and functional markers for brain health.
Gene-environment Interactions Modulating Cortical And Cognitive Dysfunction
Funder
National Health and Medical Research Council
Funding Amount
$618,300.00
Summary
A feature of many major brain disorders, including schizophrenia and dementia, is disruption of cognition. A key brain area impacted in such cognitive disorders is the prefrontal cortex. This project will use clinically translatable touchscreen to understand how this aspect of brain dysfunction causes abnormal cognition. We will investigate the mechanisms involved, using highly innovative approaches, which will contribute to the development of new treatments for such cognitive disorders.