Studies On The Biochemistry And Molecular Biology Of Amyloidosis
Funder
National Health and Medical Research Council
Funding Amount
$664,584.00
Summary
Amyloidoses are a group of diseases in which protein is abnormally deposited in various organs of the body. The prototypic amyloidosis is Alzheimer's disease (AD), a dementia causing-illness in which a protein known as Abeta is deposited in the brain. The central aim of my research is to understand the molecular etiology of AD and other amyloidoses, with a view to identifying new targets for drug development.
Identification Of Cardiac Sarcoplasmic Reticulum Targets For Cardiotoxic Drugs
Funder
National Health and Medical Research Council
Funding Amount
$265,986.00
Summary
Anthracyclines are drugs which are used successfully in chemotherapy. Unfortunately, these drugs can lead to serious heart problems which sometimes result in death, and the mechanisms behind this remain elusive. Finding the specific targets of these drugs and how these drugs affect heart contraction may lead to designing drug cocktails which protect the heart from side effects.
The Role Of Gonadotropins In Regulating The Production Of Alzheimer's Beta Amyloid
Funder
National Health and Medical Research Council
Funding Amount
$400,278.00
Summary
Currently, about 160,000 Australians suffer from dementia; of which 50-70% are Alzheimer's disease (AD) cases. AD is characterised clinically by memory and personality changes and pathologically by deposition of amyloid. Of particular importance in the disease pathogenesis, is a small molecule called beta amyloid, of which the overproduction is thought to be central to the development of AD. Changes in the levels of the reproductive hormones, particularly low levels of oestrogen during menopause ....Currently, about 160,000 Australians suffer from dementia; of which 50-70% are Alzheimer's disease (AD) cases. AD is characterised clinically by memory and personality changes and pathologically by deposition of amyloid. Of particular importance in the disease pathogenesis, is a small molecule called beta amyloid, of which the overproduction is thought to be central to the development of AD. Changes in the levels of the reproductive hormones, particularly low levels of oestrogen during menopause or testosterone during andropuase, has been associated with the increased risk of developing AD and in altering the levels of beta amyloid. Furthermore, menopause and andropause are also characterised by changes in other reproductive hormones such as the gonadotropins. High levels of the gonadotropins have also been associated with the increased risk of developing AD. Therefore it is important to identify how these changes modify the risk of developing AD. This study examines the role of the gonadotropins in regulating beta amyloid levels in cell culture and in an animal model for AD. Furthermore, this study will assess, in the animal model, the use of gonadotropin lowering agents to reduce levels of beta amyloid. The results from this study will provide important data on how reproductive hormones regulate beta amyloid. Further insight into these mechanisms will provide therapeutic or preventative strategies for AD.Read moreRead less
Effects Of Ageing On Hepatic Drug Clearance And Mechanisms Of Drug Induced Liver Disease
Funder
National Health and Medical Research Council
Funding Amount
$581,892.00
Summary
With increasing age, there is increase in disease, for which medications may provide benefit, and an increase in the risk of adverse drug reactions, even after considering the increase in medication use by older people. We will investigate how the liver clears drugs from the blood in old age. This will guide dosing of medications for older people. We will also study how drugs injure the liver in old age and test interventions to prevent this toxicity.
The research outlined in this application seeks to examine the role of calcium in the pathogenesis of AD. It will examine the hypothesis that the build-up of a protein known as the Abeta causes an increase in levels of calcium in nerve cells of the brain. This increase in calcium may trigger nerve cell damage and dementia. The ultimate aim of the research is to identify new targets for drug development in Alzheimer's disease.
Delineating The Interaction Between The Amyloid Precursor Protein Family And SorLA-LR11
Funder
National Health and Medical Research Council
Funding Amount
$749,022.00
Summary
The Alzheimer's disease Amyloid Precursor Protein (APP) is central to the cause of Alzheimer's disease (AD). It's metabolised into the neurotoxic amyloid beta (Abeta) peptide that is deposited in AD brains. The sorLA protein is a neuronal protein that interacts with APP and alters its metabolism into Abeta. This grant will study the interaction between APP and sorLA and define the APP binding site for sorLA which represents a potential drug target.
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.
Abeta Amyloid Imaging In Neurodegenerative Disorders With A Novel 18F Radiotracer
Funder
National Health and Medical Research Council
Funding Amount
$1,084,266.00
Summary
Alzheimer's disease is the most common age-related neurodegenerative disease, and the most common cause of dementia. It is estimated that 212,000 Australians suffer from dementia and this will rise to approximately 730,000 by 2050. Currently there are no definitive diagnostic methods for AD. The research proposed in this application describes the evaluation of a new imaging radiotracer that would be suitable for widespread non-invasive diagnosis of AD.
The Role Of A Presenilin 2 Truncation (PS2V) In Alzheimer's Disease
Funder
National Health and Medical Research Council
Funding Amount
$552,741.00
Summary
The Presenilin and APP proteins are centrally important in inherited, early onset Alzheimer's disease. We have discovered that a shortened form of Presenilin protein, "PS2V", appears to increase specifically the rate at which the APP protein is cleaved to produce the "Amyloid beta" protein fragment that is found in Alzheimer's disease brains. This occurs when brain cells are under oxidative stress. Understanding this process will facilitate development of appropriate therapeutic strategies for t ....The Presenilin and APP proteins are centrally important in inherited, early onset Alzheimer's disease. We have discovered that a shortened form of Presenilin protein, "PS2V", appears to increase specifically the rate at which the APP protein is cleaved to produce the "Amyloid beta" protein fragment that is found in Alzheimer's disease brains. This occurs when brain cells are under oxidative stress. Understanding this process will facilitate development of appropriate therapeutic strategies for the disease.Read moreRead less