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.
Targeting Necroptosis Signalling To Counter Stroke-induced Brain Injury
Funder
National Health and Medical Research Council
Funding Amount
$605,809.00
Summary
The origins of the brain injury that arises from stroke remain a matter of enormous interest. Our work suggests that a poorly understood form of cell death, termed necroptosis, contributes to injury to the brain following stroke. In addition to developing an advanced understanding of this process, we will use drugs developed at the Walter and Eliza Hall Institute to test whether blocking this process might be a plausible therapeutic strategy in stroke patients.
Structure-based Drug Design For Neuroprotection From Traditional Chinese Medicine
Funder
National Health and Medical Research Council
Funding Amount
$245,968.00
Summary
In the proposed research, three novo approaches for drug discovery will be explored: 1) The important neurodegenerative disease relevant protein JNK3 crystals will be used as the probe to fish out the potential inhibitors from Traditional Chinese Medicine (TCM); 2) Instead of individual drug components, the mixture of TCM will be used directly; 3) The composition of a TCM library are not randomly chosen but have been used in China for hundreds to thousands of years in curing neurodegenerative di ....In the proposed research, three novo approaches for drug discovery will be explored: 1) The important neurodegenerative disease relevant protein JNK3 crystals will be used as the probe to fish out the potential inhibitors from Traditional Chinese Medicine (TCM); 2) Instead of individual drug components, the mixture of TCM will be used directly; 3) The composition of a TCM library are not randomly chosen but have been used in China for hundreds to thousands of years in curing neurodegenerative disease.Read moreRead less
Differential Regulation Of Human Tyrosine Hydroxylase Isoforms And The Development Of Parkinson's Disease
Funder
National Health and Medical Research Council
Funding Amount
$325,591.00
Summary
Parkinson's disease is a common neurodegenerative disease whose major feature is loss of a dopamine containing nerves in a part of the brain called the substantia nigra. Loss of nerves within the substantia nigra is not uniform, but firstly and primarily affects the ventral cells, suggesting that particular dopaminergic neurons are more vulnerable to the disease process. A key to understanding Parkinson's disease would be to work out why these cells are more susceptible to degeneration than othe ....Parkinson's disease is a common neurodegenerative disease whose major feature is loss of a dopamine containing nerves in a part of the brain called the substantia nigra. Loss of nerves within the substantia nigra is not uniform, but firstly and primarily affects the ventral cells, suggesting that particular dopaminergic neurons are more vulnerable to the disease process. A key to understanding Parkinson's disease would be to work out why these cells are more susceptible to degeneration than other dopaminergic cells in the brain. Tyrosine hydroxylase controls the rate of dopamine synthesis. Humans are unique in that they contain four isoforms of tyrosine hydroxylase and therefore they have the potential to alter the regulation of dopamine synthesis in ways that other species do not. Recent developments in our laboratories have suggested that particular isoforms of tyrosine hydroxylase may have either a role in the susceptibility of dopaminergic neurons to degeneration in Parkinson's disease or a role in the timing of the symptoms of the disease. We have demonstrated differences in the distribution of the human TH isoforms within the substantia nigra, with certain isoforms being more prevalent in the susceptible ventral cells. We have also shown that there are major differences in the regulation of the four human tyrosine hydroxylase isoforms. Some isoforms will be more sensitive to conditions that occur with high frequency stimulation of neurons and some to low frequency sustained stimulation. This would provide a mechanism by which differential distribution of the human TH isoforms would result in altered dopamine synthesis in different parts of the human brain and this may in turn lead to either increased susceptibility to, or earlier appearance of symptoms of, Parkinson's disease.Read moreRead less
Site-specific Tau Phosphorylation To Treat And Understand Alzheimer’s Disease
Funder
National Health and Medical Research Council
Funding Amount
$943,902.00
Summary
Alzheimer’s disease (AD) is the most common form of dementia. Unfortunately, current therapies are ineffective. Our laboratory has made an important contribution to understanding the events that lead to brain cell malfunction in AD. I recently found a novel concept that changes the view of AD completely. In the next 3 years, I aim to develop therapeutic tools based on this novel concept and find out more about how it can protect brains from AD.