The Role Of Clusterin In Preventing Atherosclerosis
Funder
National Health and Medical Research Council
Funding Amount
$352,662.00
Summary
In atherosclerosis, plaques are formed when damaged low density lipoprotein (LDL) and fibrinogen are deposited inside blood vessels. Clusterin is a protein that stabilises damaged clients in soluble complexes, thus preventing their deposition. This project will investigate the ability of clusterin to prevent the deposition of damaged LDL and fibrinogen. Elucidation of mechanisms for preventing protein deposition will identify novel therapeutic targets for the treatment of atherosclerosis.
Counteracting Age-associated Neurodegenerative Diseases Using Chaperone-based Amyloid Disaggregases
Funder
National Health and Medical Research Council
Funding Amount
$645,205.00
Summary
In neurodegenerative diseases such as Alzheimer’s disease, proteins form clumps through changes in structure due to mutations or proteotoxic chemical insults. The formation of these toxic clumps causes brain cells to die prematurely triggering symptoms such as dementia. I have identified a molecular machine in human cells that efficiently clears these clumps. We are now developing strategies to activate this machine to repair damaged brain cells to slow/reserve neurodegenerative diseases.
The Effect Of Hypochlorite On The Toxicity And Clearance Of The Alzheimer’s Disease-associated Amyloid Beta Peptide
Funder
National Health and Medical Research Council
Funding Amount
$461,496.00
Summary
Alzheimer’s disease (AD) is the leading cause of dementia worldwide and a growing burden on our aging society. Recent studies support the idea that in AD a deleterious relationship exists between inflammation in the brain and the accumulation of amyloid beta (A?), a peptide with toxic properties. This proposal aims to examine the details of this relationship with a focus on the toxicity and clearance of A? when it is modified by hypochlortie, a chemical that is generated during inflammation.
PROTEIN TARGETS FOR THE STEROID RECEPTOR MODULATOR, CYCLOPHILIN 40
Funder
National Health and Medical Research Council
Funding Amount
$374,828.00
Summary
Steroids bind to specific receptor proteins in steroid responsive cells. These receptors are kept in a steroid-binding ready state by chaperone proteins which function to fold the receptors appropriately. The major chaperone protein is heat shock protein, hsp90. A second family of proteins called immunophilins, cooperate with hsp90 in receptor folding. These immunophilins can bind to immunosuppressant drugs, which may result in a change in receptor function. We have identified one of these immun ....Steroids bind to specific receptor proteins in steroid responsive cells. These receptors are kept in a steroid-binding ready state by chaperone proteins which function to fold the receptors appropriately. The major chaperone protein is heat shock protein, hsp90. A second family of proteins called immunophilins, cooperate with hsp90 in receptor folding. These immunophilins can bind to immunosuppressant drugs, which may result in a change in receptor function. We have identified one of these immunophilins as cyclophilin 40 ( CyP40), a protein that binds the immunosupressant drug, cyclosporin A. We have recently found that, in addition to binding to hsp90, CyP40 may bind to and regulate the function of other proteins which are important in how cells grow and die. The aims of this project are to study how CyP40 binds to hsp90 and to these other proteins and to determine the functional outcomes of these interactions.Read moreRead less