Unveiling The Origin Of Munc18-1 And Alpha-synuclein Co-aggregation At Nanoscale
Funder
National Health and Medical Research Council
Funding Amount
$620,005.00
Summary
Our recent work on Munc18-1 mutations leading to a severe form of human early infantile epileptic encephalopathy (EIEE) led us to uncover a critical role for Munc18-1 in controlling the formation of toxic protein aggregates containing ?-Synuclein. Targeting the Munc18-1 ?-Synuclein interaction may have therapeutic values not only for EIEE but also for other neurological diseases characterised by protein aggregations.
I am a neurologist and neuroscientist studying the causes and mechanisms of Parkinson's disease and the physiology in health and diseases of the nervous system affected by movement disorders
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.
Human Tyrosine Hydroxylase Isoforms And Susceptibility Of Dopaminergic Neurons To Degeneration In Parkinson's Disease
Funder
National Health and Medical Research Council
Funding Amount
$359,683.00
Summary
In Parkinson's disease there is major loss of the dopaminergic neurons of the substantia nigra. We are investigating how the control of dopamine synthesis may affect the differential loss of dopaminergic neurons in Parkinson's disease. Understanding why certain dopaminergic die in Parkinson's disease and others do not will help the development of new treatment strategies for Parkinson's disease.
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.
Neuronal Toll-like 2 Receptors Contribute To The Spread Of Parkinson's Disease
Funder
National Health and Medical Research Council
Funding Amount
$900,010.00
Summary
How the pathological protein in Parkinson’s disease (PD), ?-synuclein, spreads through the brain remains unknown. Toll-like receptor 2 (TLR2) located on microglial cells have been identified as the receptor responsible for the internalization of ?-synuclein by this cell. We have found TLR2 in PD neurons accumulating Lewy pathologies, suggesting that neuronal TLR2 contributes to the neuronal spread of ?-synuclein in PD, a theory requiring further biological evidence prior to therapeutic targeting
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
A Comparative Study Between The Effects Of C-terminally Truncated A-synuclein Metabolites And Full Length A-synuclein In Aged Rat Hippocampal Neurons
Funder
National Health and Medical Research Council
Funding Amount
$231,284.00
Summary
I am a neurologist from Xi�an Jiaotong University, China. My major research interest is in neurodegenerative diseases, especially Parkinson and Alzheimer�s disease. I enter this field because I know ageing population will have an enormous impact on the world�s economy. I started collaboration with Dr. Weiping Gai in Flinders University. We are interested in the toxic effects of both a-synuclein and its metabolites, their mechanisms and ways to block them.