Proteolytic Processing Of Alzheimer's Amyloid Precursor: Identification Of Gamma-secretase
Funder
National Health and Medical Research Council
Funding Amount
$240,581.00
Summary
Alzheimer's disease is the major cause of dementia among the elderly and affects more than 20% of the population aged 80 and over. There is no cure for the disease and the treatments currently available can only retard its progression and have serious side-effects. Examination of the brain from subjects who died from Alzheimer's disease shows lesions: these are called amyloid plaques. The plaques are formed by the abnormal accumulation of an insoluble and toxic protein which causes death of the ....Alzheimer's disease is the major cause of dementia among the elderly and affects more than 20% of the population aged 80 and over. There is no cure for the disease and the treatments currently available can only retard its progression and have serious side-effects. Examination of the brain from subjects who died from Alzheimer's disease shows lesions: these are called amyloid plaques. The plaques are formed by the abnormal accumulation of an insoluble and toxic protein which causes death of the brain cells. Some gene defects which cause Alzheimer's disease at an early age (30-60 years) are known to accelerate the accumulation of the toxic protein, thereby causing progressive degeneration of the brain. Our research is aimed at understanding at the molecular level how the toxic protein forms. We know that it is part of a large protein and that its release requires two enzyme cuts. Now we propose to isolate and characterize these enzymes and to search for drugs which will neutralize them. This constitutes a rational approach to a therapeutic strategy fo halting or slowing down the progression of Alzheimer's disease.Read moreRead less
Molecular Characterization Of The Gingipains Of Porphyromonas Gingivalis
Funder
National Health and Medical Research Council
Funding Amount
$394,000.00
Summary
Chronic periodontitis is a bacteria-associated inflammatory disease of the supporting tissues of the teeth, which results in the destruction of tooth support and ultimately leads to tooth loss. The disease is a major public health problem with a large economic burden and has been associated with an increased risk of cardiovascular disease and pre-term birth and low birth weight. The bacterium Porphyromonas gingivalis has now been identified as a major pathogen in the development of chronic perio ....Chronic periodontitis is a bacteria-associated inflammatory disease of the supporting tissues of the teeth, which results in the destruction of tooth support and ultimately leads to tooth loss. The disease is a major public health problem with a large economic burden and has been associated with an increased risk of cardiovascular disease and pre-term birth and low birth weight. The bacterium Porphyromonas gingivalis has now been identified as a major pathogen in the development of chronic periodontitis. We have identified a major virulence factor of P. gingivalis which is an extracellular complex of proteins involved in binding and destroying host proteins. The aim of this proposal is to characterize the secretion, molecular processing and assembly of the cell surface complex using state-of-the-art proteomic techniques. This study will provide valuable insight into the molecular processes of a bacterial pathogen that leads to virulence. Detailed knowledge on the unique molecular events involved in secretion, processing and assembly of a major virulence factor will provide molecular targets for the development of specific inhibitors that may have utility as an adjunctive therapeutic and-or as part of a preventive regime or maintenance program for the control of chronic periodontitis. Further, the molecular insight that will result from this study will have broader application in the understanding of virulence factor processing of a Gram-negative pathogen that will provide paradigms for other bacterial pathogens.Read moreRead less
In the normal process of hearing, the brain actively selects sounds of interest from competing background sounds. This normal auditory function is indispensible for children and adults to cope in non-optimal listening environments, however the mechanisms by which such performance is achieved are poorly understood. This project will investigate the nerve circuits that enable this to occur and will also investigate how these circuits malfunction in various types of partial deafness. The results wi ....In the normal process of hearing, the brain actively selects sounds of interest from competing background sounds. This normal auditory function is indispensible for children and adults to cope in non-optimal listening environments, however the mechanisms by which such performance is achieved are poorly understood. This project will investigate the nerve circuits that enable this to occur and will also investigate how these circuits malfunction in various types of partial deafness. The results will improve our understanding of how we detect sounds and the impact of hearing pathologies on this process.Read moreRead less