Understanding the biological mechanisms of nerve degeneration is an essential step toward the development of novel therapies for human neurodegenerative conditions such as Parkinson's, Alzheimer's and Huntington's diseases, and for spinal cord injuries. The studies presented in this proposal, using the powerful molecular and genetic tools available for the small nematode worm C. elegans, will provide new insights into the cellular and molecular mechanisms responsible for nerve degeneration.
Role Of Osteopontin In Ischemic-like Injury To The Retina
Funder
National Health and Medical Research Council
Funding Amount
$357,862.00
Summary
The molecule osteopontin (OPN) is implicated in the response of certain tissues to disease. We have new evidence that the level of OPN in the visual retina increases markedly following injury. We hypothesise that OPN is produced by specialised retinal cells in response to injury and functions to promote the survival of nerve cells. The proposed research seeks to investigate this hypothesis and the results will contribute to a greater understanding of the role of OPN in retinal diseases.
The Role Of Glutamate Receptor Mediated Excititoxicity In Neurodegeneration And Huntington's Disease
Funder
National Health and Medical Research Council
Funding Amount
$467,310.00
Summary
Glutamate, the principal excitatory neurotransmitter in the brain, acts on three subtypes of ionotropic glutamate receptors (iGluRs), AMPA, kainate and NMDA receptors. Evidence suggests that aberrant NMDA receptor mediated calcium influx into neurons leads to excitotoxic cell death. Calcium influx through AMPA and kainate receptors has also been implicated in excitotoxic neurodegeneration. It is widely thought that excitotoxicity contributes to chronic neurodegenerative disease. We will test thi ....Glutamate, the principal excitatory neurotransmitter in the brain, acts on three subtypes of ionotropic glutamate receptors (iGluRs), AMPA, kainate and NMDA receptors. Evidence suggests that aberrant NMDA receptor mediated calcium influx into neurons leads to excitotoxic cell death. Calcium influx through AMPA and kainate receptors has also been implicated in excitotoxic neurodegeneration. It is widely thought that excitotoxicity contributes to chronic neurodegenerative disease. We will test this hypothesis by investigating degeneration in mutant mice with altered iGluR mediated calcium flux alone and combined with mutant genes known to cause Huntington s disease by: knocking-out the NMDA receptor in select brain regions of mice and determining if that protects against neurodegenerative pathology in those brain regions. generating mutant mice with kainate or AMPA-Rs that flux abnormally high amounts of calcium and determine if that predisposes the mouse brains to neurodegenerative pathology. These experiments will provide valuable animal models enabling a deeper understanding of neurodegenerative processes. The models will also provide invaluable resources for developing therapies to protect against neurodegeneration.Read moreRead less
Development And Refinement Of Neural Connections In The Adult Brain In Health And Disease
Funder
National Health and Medical Research Council
Funding Amount
$8,061,596.00
Summary
Our group will use innovative approaches such as advanced imaging and cell-sorting and development of animal models to determine how new neurons are generated, how they travel to different parts of the brain and how they integrate into the existing brain circuitry. These discoveries will point to new ways in which to treat brain damage both during ageing and during pathology. Since team members have previously been involved in progressing molecular discovery to clinical trials, we are also in a ....Our group will use innovative approaches such as advanced imaging and cell-sorting and development of animal models to determine how new neurons are generated, how they travel to different parts of the brain and how they integrate into the existing brain circuitry. These discoveries will point to new ways in which to treat brain damage both during ageing and during pathology. Since team members have previously been involved in progressing molecular discovery to clinical trials, we are also in a good position to exploit these discoveries in partnership with the biopharmaceutical industry.Read moreRead less
A -induced Cell Death Signalling By The P75 Neurotrophin Receptor.
Funder
National Health and Medical Research Council
Funding Amount
$546,382.00
Summary
The amyloid peptide A is central to the cause of Alzheimer's disease. We have recently found that A can activate the cell death receptor p75NTR which is found in the nerve cells that die in Alzheimer's disease. This project will study whether this death pathway underpins the neuronal death associated with Alzheimer's disease. It will also determine the mechanism by which A activates p75NTR death signalling, and identify biochemical ways to prevent this from occurring.