Pathogenic And Adaptive Molecular Interactions With Mutant Huntingtin Exon 1
Funder
National Health and Medical Research Council
Funding Amount
$727,117.00
Summary
This project aims to determine how the gene mutation that causes Huntington’s disease (HD) damages cells in the brain. The diseased gene creates a protein that is abnormally sticky, which causes it to form clumps. Our goal is to determine the components of the cell that are disrupted and damaged as clumping happens. Understanding this link will enable therapeutics to be logically designed in efforts to prevent harm to the brain, potentially before symptoms are evident.
The Role Of Copper In Ubiquitin-dependent Protein Degradation In Alzheimer's Disease
Funder
National Health and Medical Research Council
Funding Amount
$588,622.00
Summary
Ubiquitin’s are small proteins that tag other proteins in a process known as “Ubiquitination”. Often this is to target them for degradation once they are no longer needed i.e. to take out the rubbish. This process is disrupted in Alzheimer’s disease (AD), which may contribute to the disease. This project aims to find out if copper, an essential metal for life, is required for this process. Drugs that are designed to deliver copper to brain cells have been effective in small AD clinical trials.
Regulation Of Synaptic Vesicle Biogenesis For Synaptic Transmission
Funder
National Health and Medical Research Council
Funding Amount
$339,115.00
Summary
The overall aim is to better understand the molecular processes of nerve cell communication during learning, memory and abnormal brain activity that cause neurological diseases. The supply and generation (biogenesis) of synaptic vesicles (SVs) in nerve cells is critical to sustain neurotransmission. It requires complex protein interactions and signalling. Thus modulation of SV biogenesis at the molecular level will allows future development of new targeted treatments for neurological diseases.
Regulation of Stress Hormone Receptors in the Brain. Our research will provide information on how the brain controls our response to stress and will allow the development of targeted strategies to reduce the possibility during chronic stress of the development of conditions such as anxiety and depression. This will improve mental health outcomes in Australia and add to Australia's economic and social stability.
Neurons are highly compartmentalized cell-types. In neurodegenerative diseases such as Alzheimer's disease, the protein Tau that serves a distinct function in one cellular compartment (the axon) accumulates in a massively phosphorylated form elsewhere (somatodendritic compartments and their spines) which is believed to impair neuronal functions. We will investigate how Tau is distributed in health and disease, and determine how this distribution is regulated.
Single minded 1 in neuron development and satiety signalling. An understanding of how Single minded 1 (SIM1) regulates target genes may allow new pharmaceutical approaches to be designed to combat obesity. As Sim1 belongs to a family of closely related gene regulatory proteins which function in early development and homeostasis, deciphering the molecular control mechanisms of Sim1 may help understand how the related factors function in processes such as angiogenesis, response to low oxygen stres ....Single minded 1 in neuron development and satiety signalling. An understanding of how Single minded 1 (SIM1) regulates target genes may allow new pharmaceutical approaches to be designed to combat obesity. As Sim1 belongs to a family of closely related gene regulatory proteins which function in early development and homeostasis, deciphering the molecular control mechanisms of Sim1 may help understand how the related factors function in processes such as angiogenesis, response to low oxygen stress, invasion of environmental pollutants and autism spectrum diseases. The ability to manipulate these factors would be of great benefit in treating a range of disorders, but a thorough molecular understanding of these factors needs be obtained prior to attempting design of pharmaceuticals.Read moreRead less
Cellular Pathogenesis Of Neurodegenerative Disorders
Funder
National Health and Medical Research Council
Funding Amount
$124,530.00
Summary
Alzheimer's disease is the most common neurodegenerative disease of the ageing population and is associated with toxicity of the Abeta peptide. Prion diseases (eg CJD in humans) are infectious neurodegenerative disorders caused by misfolding of the prion protein. This proposal aims to bring together similar features of these diseases using novel cell and animal based studies to develop better diagnostics and greater understanding of the molecular basis of these disorders with a view to developin ....Alzheimer's disease is the most common neurodegenerative disease of the ageing population and is associated with toxicity of the Abeta peptide. Prion diseases (eg CJD in humans) are infectious neurodegenerative disorders caused by misfolding of the prion protein. This proposal aims to bring together similar features of these diseases using novel cell and animal based studies to develop better diagnostics and greater understanding of the molecular basis of these disorders with a view to developing interventional therapies.Read moreRead less
Protein Phosphatase 2A Methylation: Regulation And Functional Significance For Tauopathies
Funder
National Health and Medical Research Council
Funding Amount
$470,713.00
Summary
Clinical studies have revealed that low blood levels of the vitamin folate are a risk factor for cognitive impairment, depression and dementia, which are prevalent in the elderly. Deregulation of the protein tau is a key event in Alzheimer’s disease pathogenesis. This project will utilize cell culture and aged mouse models to determine how alterations in folate status and deregulation of protein phosphatase 2A affect the regulation of tau and other key brain processes that become altered in Alzh ....Clinical studies have revealed that low blood levels of the vitamin folate are a risk factor for cognitive impairment, depression and dementia, which are prevalent in the elderly. Deregulation of the protein tau is a key event in Alzheimer’s disease pathogenesis. This project will utilize cell culture and aged mouse models to determine how alterations in folate status and deregulation of protein phosphatase 2A affect the regulation of tau and other key brain processes that become altered in Alzheimer’s disease.Read moreRead less
How Alzheimers-associated Cytoskeletal Inclusions Form Road Blocks And Impair Trafficking In Neurons
Funder
National Health and Medical Research Council
Funding Amount
$351,181.00
Summary
This research is aimed at delineating basic mechanisms of nerve cell dysfunction relevant to Alzheimer's disease and other dementias with the goal of achieving a positive impact into understanding the causes of these diseases. The outcomes of the project will identify pathways involved in generating pathological changes in nerve cells and will therefore facilitate the development of targeted therapies, ultimately improving the outlook for Alzheimer's patients and the community.