Sortilin Forms A Complex With APP And BACE To Regulate Abeta Production
Funder
National Health and Medical Research Council
Funding Amount
$208,910.00
Summary
Alzheimer's disease is a neurodegenerative disorder which is highly prevalent in aging population. Amyloid beta is a toxic peptide derived from a metabolic processing of its precursor amyloid precursor protein (APP). This project will examine how a novel protein called sortilin interacts with APP and its processing enzyme and how the toxic peptide is produced. Understanding the trafficking of APP and beta-secretase ?BACE? regulated by sortilin may help understanding how Alzheimer's disease is de ....Alzheimer's disease is a neurodegenerative disorder which is highly prevalent in aging population. Amyloid beta is a toxic peptide derived from a metabolic processing of its precursor amyloid precursor protein (APP). This project will examine how a novel protein called sortilin interacts with APP and its processing enzyme and how the toxic peptide is produced. Understanding the trafficking of APP and beta-secretase ?BACE? regulated by sortilin may help understanding how Alzheimer's disease is developed.Read moreRead less
Use Of The P75NTR Extracellular Domain As A Therapeutic Target For The Treatment Of Alzheimer's Disease
Funder
National Health and Medical Research Council
Funding Amount
$733,633.00
Summary
AlzheimerÍs disease is the most common form of dementia and is caused by both environmental and genetic variations. With aging, a toxic peptide accumulates in the brain and causes loss of memory and cell death. This study aims to elucidate how the toxic peptide is generated and how to remove it in order to prevent and treat the disease.
Deciphering the cellular defences against aggregating proteins in human disease. Cells have inbuilt defences for coping with proteins that bend into abnormal sticky shapes that form toxic clusters. In many diseases, including Huntington's, the clusters severely damage nerve cells. This project will identify the genes and mechanisms cells use to protect themselves from toxic clusters, which could provide new therapeutic targets.
Cell Trafficking In A Stem Cell Model For Hereditary Spastic Paraplegia
Funder
National Health and Medical Research Council
Funding Amount
$524,082.00
Summary
Hereditary Spastic Paraplegia (HSP) is a genetic disease passed down in affected families. It is a slowly progressing lower limb paralysis that gradually restricts daily activities until the sufferer is confined to bed. There are no cures. This project investigates patientsÍ stem cells to study how HSP genes cause disease. We will use these stem cells to discover new potential drug therapies.
Dysferlin And The Emergency Vesicle Fusion Of Membrane Repair
Funder
National Health and Medical Research Council
Funding Amount
$481,496.00
Summary
Membrane repair is a vital cell survival mechanism of all eukaryotic cells, using calcium-triggered vesicle fusion to ‘patch’ membrane ruptures. The muscular dystrophy protein dysferlin is a key mediator of membrane repair, although, exactly how dysferlin mends membranes has been unclear. We show that the calcium that floods through membrane tears, activates a group of enzymes called calpains, that specifically cleave dysferlin to release a specialist vesicle-fusion module for membrane repair.
Disruption To Intracellular Trafficking As A Central Pathogenic Mechanism In Amyotrophic Lateral Sclerosis (ALS)
Funder
National Health and Medical Research Council
Funding Amount
$688,157.00
Summary
There are several different forms of ALS (MND), but the disease appears very similar in terms of symptoms and pathology. We have identified a common disease process shared by several different forms of ALS, which suggests that this is the underlying mechanism by which motor neurons die. This study will investigate whether we can develop new drug targets based on this mechanism in animal disease models. This may ultimately assist in the development of new treatments for ALS.
Neuroprotective Functions Of Autophagy Regulators In Alzheimer's Disease
Funder
National Health and Medical Research Council
Funding Amount
$434,644.00
Summary
The accumulation of the beta amyloid protein has a central role in AD and enhancing its removal improves memory loss in animal AD models. This project builds on my recent finding of regulators of a cell housekeeping system, “autophagy” which accelerate removal of beta amyloid in cells. This study will advance knowledge into the protective functions of the autophagy regulators in reducing AD symptoms. Findings from this work might provide the basis for developing effective anti-AD therapeutics.
Dysferlinopathy: A Genetic Disease Sheds Light On Membrane Repair For Muscle And Cardiac Injury
Funder
National Health and Medical Research Council
Funding Amount
$782,806.00
Summary
Muscles are damaged all of the time, as we stretch and contract them, but we don't fully understand how they repair themselves. We are studying the molecular steps taken by a muscle cell to repair membrane damage. Our research will provide valuable insights into how to treat muscular dystrophy and other conditions characterised by membrane damage to cells, such as heart attack and stroke.
Dysferlin Coordinates Membrane Repair For Skeletal And Cardiac Injury
Funder
National Health and Medical Research Council
Funding Amount
$459,270.00
Summary
Muscles are damaged all of the time, as we stretch and contract them, but we don't fully understand how they repair themselves. We are studying the molecular steps taken by a muscle cell to repair membrane damage. Our research will provide valuable insights into how to treat muscular dystrophy and other conditions characterised by membrane damage to cells, such as heart attack and stroke.
A Role Of Sortilin In The Development Of Alzheimer's Disease
Funder
National Health and Medical Research Council
Summary
Alzheimer’s disease is the most common form of dementia and is caused by both environmental and genetic variations. With aging, a toxic peptide accumulates in the brain and causes loss of memory and cell death. This study aims to elucidate how the toxic peptide is generated and how its precursor trafficks within nerve cells.