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.
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.
Genetic Mechanisms That Moderate Effects Of Aβ Accumulation In Preclinical Alzheimer's Disease
Funder
National Health and Medical Research Council
Funding Amount
$603,525.00
Summary
Alzheimer’s disease (AD) is the most common form of dementia, and the number of people living with it will triple by 2050. There is currently no cure for AD, and the only means of slow the growing epidemic is to delay onset. We propose to understand the complex interplay between genetic, cognitive, neuroimaging and biological markers of AD in order to better understand the disease process, and in turn identify high-risk individuals for clinical trials and uncover disease-modifying strategies.
IRON EXPORT PROTEIN FAILURE IN PARKINSONISM AND DEMENTIA
Funder
National Health and Medical Research Council
Funding Amount
$843,352.00
Summary
We recently discovered a novel relationship between the Alzheimer’s amyloid precursor protein (APP) and tau, and that both proteins play a role in regulating iron levels in the brain. We predict that a loss or multiple failures in these iron-regulating systems could foster a toxic iron accumulation in brain, leading to the development of diseases with dementia such as Alzheimer’s and Parkinson’s diseases. We hope to gain a better understanding of their mechanism of action and propose that this p ....We recently discovered a novel relationship between the Alzheimer’s amyloid precursor protein (APP) and tau, and that both proteins play a role in regulating iron levels in the brain. We predict that a loss or multiple failures in these iron-regulating systems could foster a toxic iron accumulation in brain, leading to the development of diseases with dementia such as Alzheimer’s and Parkinson’s diseases. We hope to gain a better understanding of their mechanism of action and propose that this pathway is a target for therapeutic intervention.Read moreRead less
Implications Of Retinal Neurodegeneration In Alzheimer's Disease
Funder
National Health and Medical Research Council
Funding Amount
$602,213.00
Summary
Recent research has shown that “early signs” of Alzheimer ’s disease (AD) can be detected in the eyes. My research focus is to determine which particular changes in the retina are associated with AD. I will also investigate if blocking the production of beta amyloids (proteins produced in AD) in the eye will indeed help reduce their load in the brain and hence delay the onset of AD. Results from this research maybe used for early diagnosis and future medicinal studies that target the eye in AD.
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.
Preclinical Evaluation Of The Novel Therapeutic Compound APP96-110 In An Ovine Model Of Traumatic Brain Injury
Funder
National Health and Medical Research Council
Funding Amount
$874,734.00
Summary
Traumatic brain injury (TBI) is a significant cause of death and disability, and yet there are currently no effective treatments to improve outcome following such an insult. Our laboratory has developed a novel therapeutic compound, by identifying an endogenous neuroprotective molecule, in the amyloid precursor protein and then identifying the active site and modifying it to improve its efficacy. We will be testing this compound in our sheep model of TBI.
The Characterisation Of The Mechanism Of Beta Amyloid Toxicity In Alzheimer's Disease
Funder
National Health and Medical Research Council
Funding Amount
$94,430.00
Summary
Alzheimer�s disease (AD) is the most common form of dementia and is characterised by the beta amyloid peptide (A_) found in plaques in the brain. A structural transition to aggregated/ oligomeric forms of A_ is accompanied by a gain of toxicity. In this study the biological and biophysical characterisation of a variety of A_ peptides will be performed. The study will also use oligomers from cell culture media and brain tissue that have been influential in AD research but poorly characterised.
The Pathway Linking Tau And APP In Neurodegeneration
Funder
National Health and Medical Research Council
Funding Amount
$312,085.00
Summary
Recently I co-discovered a novel relationship between the AlzheimerÍs amyloid precursor protein and tau, both of which play a role in regulating neuronal iron levels. I predict that multiple failures in iron-regulating systems could foster a toxic iron accumulation in brain, leading to the development of neurodegenerative diseases. I hope to gain a better understanding of their mechanism of action and propose that this pathway is a target for therapeutic intervention.