Testing The Prion Hypothesis In Parkinson’s Disease Using A Novel In Vivo Model Of Α-synuclein Transmission
Funder
National Health and Medical Research Council
Funding Amount
$622,555.00
Summary
Parkinson’s Disease (PD) is a debilitating neurological disease with no cure. Recently it has been discovered that the disease can spread through the brain. We have developed the worlds first animal model to study exactly how the disease propagates inside of neurons during this spread. We will use the model to answer key questions about this critical stage of disease spread, knowledge that is essential for the development of successful therapies to prevent disease progression.
Glia And The Progression Of Parkinson's Disease: Bystanders Or Villains?
Funder
National Health and Medical Research Council
Funding Amount
$534,838.00
Summary
Parkinson's disease (PD) is a chronic and progressive neurodegenerative disease with no cures or effective treatments. We know where in the brain PD begins but how it spreads to affect more and more cells is unknown. This lack of understanding has been a barrier to treatment development. In this project we will use new models that will enable unprecedented insight into this process of disease spreading, and in doing so will reveal new targets for therapeutic development.
Investigation Of The Molecular Mechanisms Underlying Alpha Synuclein Function At The Presynapse
Funder
National Health and Medical Research Council
Funding Amount
$419,180.00
Summary
Parkinson’s Disease (PD) is a common brain disease affecting 7 million people worldwide. It is caused by the death of brain cells. ?-synuclein is a protein in that brain that is likely to contribute to the cell death in PD, but the normal role of the protein remains unknown. This study will investigate the function of ?-synuclein in maintaining normal healthy brain activity. In addition, this work will help us understand how normal brain processes are affected in diseases such as PD.
Investigating Biometal Dyshomeostasis In Dementia With Lewy Bodies
Funder
National Health and Medical Research Council
Funding Amount
$554,644.00
Summary
Dementia with Lewy bodies (DLB) is the second most common form of dementia after Alzheimer's disease (AD). Very little is known about what causes DLB and there are currently no effective therapeutics. An imbalance in naturally occurring biological metals such as iron and copper have been implicated in AD and Parkinson’s disease so this project will investigate if metals are involved in DLB. The ultimate goal of this project is to identify if metals are a valid target for future drug development.
Isoprenoids, Neuromelanin And Neuronal Vulnerability In Parkinson's Disease
Funder
National Health and Medical Research Council
Funding Amount
$538,764.00
Summary
Parkinson's disease is a common and ultimately fatal brain disease which affects primarily normal movement. While a comparatively modest cell death occurs in other areas of the brain in Parkinson's disease, the motor symptoms result from the massive death of particular brain cells which are unique in that they contain a pigment called neuromelanin. This project aims to discover what makes the neuromelanin-containing cells of the brain particularly vulnerable to cell death in Parkinson's disease. ....Parkinson's disease is a common and ultimately fatal brain disease which affects primarily normal movement. While a comparatively modest cell death occurs in other areas of the brain in Parkinson's disease, the motor symptoms result from the massive death of particular brain cells which are unique in that they contain a pigment called neuromelanin. This project aims to discover what makes the neuromelanin-containing cells of the brain particularly vulnerable to cell death in Parkinson's disease. We recently found that neuromelanin pigment in the cells of people who have died with Parkinson's disease concentrate a fat-binding protein called alpha-synuclein which is thought to be important in causing cell death in Parkinson's disease. This association between the neuromelanin pigment and alpha-synuclein was not found in other cells in Parkinson brain which do not contain pigment, nor in the brains of healthy people. We also found that a third of neuromelanin is made up of a special group of fats called isoprenoids. Changes in these fats have already been reported in the blood in Parkinson's disease. We suggest that specific changes in the isoprenoid fats in neuromelanin in Parkinson's disease cause alpha-synuclein protein to accumulate on the fat in the pigment, as well as other cellular changes which are detrimental to the cell, ultimately leading to the death of the cell. These changes may explain for the first time why neuromelanin-containing brain cells are especially vulnerable in Parkinson's disease and provide new avenues for treating this disorder.Read moreRead less
Trials of numerous agents to slow the progression of Parkinsons disease have provided ambiguous or negative results despite having good preliminary evidence for their efficacy. The most likely reason is that many nerve cells are already destroyed by the time of diagnosis. Thus effective therapies may be most (and possible only) effective when administered in the presymptomatic stages of disease. This proposal is directed at developing method to detect early presymptomatic Parkinsons disease.
The Functional Interplay Between Alpha Synuclein And Synaptophysin In Synaptic Vesicle Recycling
Funder
National Health and Medical Research Council
Funding Amount
$405,461.00
Summary
Parkinson’s Disease (PD) is the second most common neurodegenerative disorder, affecting 7 million people worldwide. ?-synuclein is a protein in that brain that is likely to contribute to the death of brain cells in PD, but the normal role of the protein remains unknown. This study will investigate the function of ?-synuclein in maintaining normal healthy brain activity. In addition, this work will help us understand the processes that go awry in neurodegenerative disease states such as PD.
Nerodegeneration In The Aging Brain: How The Pathways Leading To Aggregating Protein Cause Disease
Funder
National Health and Medical Research Council
Funding Amount
$15,050,508.00
Summary
The Neurodegeneration Program is discovering the basic pathways that cause Alzheimer’s disease and related diseases of the aging brain; from these discoveries the team are finding new methods for early diagnosis and therapeutic interventions which will allow them to determine whether it is possible to delay the onset or improve the way in which the brain copes with these diseases
The Role Of Long Noncoding RNAs In Parkinson’s Disease
Funder
National Health and Medical Research Council
Funding Amount
$692,699.00
Summary
Parkinson's disease is a complex neurodegenerative disorder. For 90% of patients there is no known cause and for all patients there is no cure. The development of genome studies and transcriptome sequencing has revealed a class of noncoding RNAs whose regulation or dysregulation may lay at the heart of what goes wrong for PD sufferers. Our laboratory focuses on critical PD genes and their regulation by long noncoding RNAs.
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.