Gene-environment Interactions Modulating Cognition And Dementia In Huntington’s Disease
Funder
National Health and Medical Research Council
Funding Amount
$394,425.00
Summary
We are investigating mechanisms whereby cognitive symptoms, culminating in dementia, occur in a fatal brain disease, Huntington’s. We will explore how the ‘genetic stutter’ affects the brain at the level of molecules and cells, which will help identify targets for future treatment. We will also establish how environmental factors, including cognitive stimulation, physical activity and stress, modulate dementia. This will inform the development of treatments for this currently incurable disease.
The Role Of PARK9 And Autophagy In Parkinson's Disease.
Funder
National Health and Medical Research Council
Funding Amount
$396,198.00
Summary
With an ageing population, the health burdens of neurodegenerative diseases such as Parkinson's disease (PD) are numerous. We have found a role for a PD suspectibility gene, PARK9, in autophagy- a neuroprotective degradative pathway, that may also be involved in keeping ÎSyn, a pivitol protein in PD, levels in check.
Huntington’s disease (HD) is a devastating neurodegenerative disorder which shares several features with Alzheimer’s and Parkinson’s disease (i.e. dementia-like cognitive deficits). There is currently no cure for HD. Using a mouse model of HD and a combination of relevant drugs (i.e. N-Acetylcysteine and deferiprone) targeting two distinct levels of the cascade of events leading to HD, we will slow down the progression of the disease and correct dysfunctions within the brain.
A Randomised Controlled Trial Of Physical Activity With Individual Goal-setting And Volunteer Mentors To Overcome Sedentary Lifestyle In Older Adults At Risk Of Cognitive Decline
Funder
National Health and Medical Research Council
Funding Amount
$506,405.00
Summary
Thirteen percent of all cases with Alzheimer’s Disease are potentially due to a lack of physical activity. This study investigates whether a 6-month physical activity program can significantly increase physical activity levels in older adults who are concerned about their memory and who are not physical active. New about this trial is that participants can choose their own goals they want to reach and the additional involvement of physical active volunteers who will support the participants.
Dissecting The Role Of RYK In Cortical Neuron Specification And Schizophrenia
Funder
National Health and Medical Research Council
Funding Amount
$1,039,028.00
Summary
Correct production of neuronal subtypes within the neocortex is essential for coordinated brain activity and higher-order functions. Understanding how newborn neurons decide which subtype to adopt is critical as incorrect neuron identity has profound consequences for neocortical function and is associated with schizophrenia and mental disability. We have recently linked one molecule, RYK, to schizophrenia. In this project we will explore how Ryk influences cortical neuron fate.
Novel Epidemiological Methods To Infer The Causal Effects Of Risk Factors On Neuropsychiatric And Cardiovascular Disorders
Funder
National Health and Medical Research Council
Funding Amount
$182,003.00
Summary
Epidemiological studies, which associate risk factors and disease, are central in informing public health policy. Because causality is difficult to ascertain from these associations, public health interventions based on these findings are at some risk of failure. We propose to develop, extend and apply an innovative epidemiological approach, Mendelian randomization (MR) to resolve the causal relationship between risk factors and neuropsychiatric and cardiovascular disorders.
Impaired Mitochondrial Energy Metabolism And The Therapeutic Activity Of Cu(atsm) In Age And Age-related Neurodegenerative Disease
Funder
National Health and Medical Research Council
Funding Amount
$689,823.00
Summary
Cognitive function and locomotor ability decline due to advanced age and disorders such as motor neuron disease, Alzheimer’s and Parkinson’s disease. We have identified a treatment that attenuates these symptoms of age and disease in mice, thus extending the healthy lifespan of the animals. This project will investigate the mechanisms by which the treatment works, thereby advancing our understanding of the causes of cognitive and locomotor decline and the development of preventative treatments.
Using High-throughput Genomics To Reveal The Deleterious Genetic Changes That Underlie Paediatric Leukoencephalopathies
Funder
National Health and Medical Research Council
Funding Amount
$1,003,712.00
Summary
There has been an explosion of high-throughput DNA sequencing technologies in the past five years, which have the potential to completely revolutionise medicine and scientific research. Here we present a series of studies showing the successful application of this technology to children with genetic disorders of the central nervous system. This proposal seeks to expand this study to a large cohort of similarly affected paediatric patients.
Copper Pathways Are Altered In Parkinson’s Disease: Implications For Cell Vulnerability
Funder
National Health and Medical Research Council
Funding Amount
$341,398.00
Summary
The cause of brain cell death in Parkinson’s disease is unknown but we have shown that copper levels are reduced in the vulnerable brain regions in this disorder. As copper is vital for the normal function of key brain proteins we suggest that reduced copper contributes to cell damage in vulnerable brain regions. This project investigates why brain copper levels are reduced in the Parkinson’s disease brain and the consequences of this change for brain cell function and survival.
How Do Small Extracellular Vesicles Contribute To The Development Of Prion Disease
Funder
National Health and Medical Research Council
Funding Amount
$563,897.00
Summary
Prion diseases are transmissible neurodegenerative disorders associated with the misfolding of the prion protein. This proposal will investigate how cells release the infectious agent responsible for prion diseases in small nanovesicles known as exosomes. We will characterise the novel processed forms of the proteins involved in these two neurodegenerative diseases within the exosomes and investigate whether the genetic content of exosomes has diagnostic potential.