How Alzheimers-associated Cytoskeletal Inclusions Form Road Blocks And Impair Trafficking In Neurons
Funder
National Health and Medical Research Council
Funding Amount
$351,181.00
Summary
This research is aimed at delineating basic mechanisms of nerve cell dysfunction relevant to Alzheimer's disease and other dementias with the goal of achieving a positive impact into understanding the causes of these diseases. The outcomes of the project will identify pathways involved in generating pathological changes in nerve cells and will therefore facilitate the development of targeted therapies, ultimately improving the outlook for Alzheimer's patients and the community.
The Effect Of Metals On Neurofibrillary Tangle Formation
Funder
National Health and Medical Research Council
Funding Amount
$333,313.00
Summary
The majority of studies into Alzheimer's disease (AD) have focussed on two brain lesions- the plaque and neurofibrillary tangle (NFT), which are believed to have a causative role in AD. Our lab has made several seminal discoveries about the role that metals play in the development of plaques. We are now extending this work to evaluate the role of metals in NFT formation. These studies will provide insight into the formation and possible treatments for this primary brain lesion in AD.
Lipid Rafts, Amyloid Neurotoxicity And Alzheimer's Disease
Funder
National Health and Medical Research Council
Funding Amount
$318,267.00
Summary
Alzheimer's disease is the major cause of dementia in the elderly. Individuals with Alzheimer's disease exhibit a slow decline in cognition which usually results in prolonged institutionalisation. This creates an enormous burden on society. The project aims to identify mechanisms which cause Alzheimer's disease. Specifically, it will examine how a component of the brain, known as the amyloid protein, contributes to nerve cell degeneration. It is hoped that by identifying these mechanisms, new ta ....Alzheimer's disease is the major cause of dementia in the elderly. Individuals with Alzheimer's disease exhibit a slow decline in cognition which usually results in prolonged institutionalisation. This creates an enormous burden on society. The project aims to identify mechanisms which cause Alzheimer's disease. Specifically, it will examine how a component of the brain, known as the amyloid protein, contributes to nerve cell degeneration. It is hoped that by identifying these mechanisms, new targets for drug development will be found.Read moreRead less
Function Of A Novel Interferon In Reproductiona And Development
Funder
National Health and Medical Research Council
Funding Amount
$507,270.00
Summary
It is important to understand the factors responsible for maintaining fertility, pregnancy and to prevent infection of the developing fetus and the uterus. The latter is an important general problem in women. We have identified a new protein that our current evidence suggests is involved in reproduction, embryonic or fetal development. This new protein is related tot he interferon family of proteins that are best characterised by their important functions in protecting the host from viral infect ....It is important to understand the factors responsible for maintaining fertility, pregnancy and to prevent infection of the developing fetus and the uterus. The latter is an important general problem in women. We have identified a new protein that our current evidence suggests is involved in reproduction, embryonic or fetal development. This new protein is related tot he interferon family of proteins that are best characterised by their important functions in protecting the host from viral infections and cancer. We propose to undetake a detailed study to determine when and where the new interferon is produced in the reproductive tract and during pregnancy and its importance in the maintenance of pregnancy and in protection against fetal-uterine infection.Read moreRead less
Alzheimer's Disease And Related Disorders: Mechanism Of Tau Pathology In Established And Novel Transgenic Animal Models
Funder
National Health and Medical Research Council
Funding Amount
$423,017.00
Summary
Alzheimer's disease (AD) is a devastating neurodegenerative disease for which no cure is available. It affects more than 15 million people worldwide. There are estimates that by 2040, approximately 500'000 Australians will suffer from AD, with associated health costs of about 3% of the GDP. AD is characterized by two major brain lesions, beta-amyloid plaques and neurofibrillary tangles (NFTs). The latter contain a protein called tau which is in a fibrillar and highly phosphorylated state. We wer ....Alzheimer's disease (AD) is a devastating neurodegenerative disease for which no cure is available. It affects more than 15 million people worldwide. There are estimates that by 2040, approximately 500'000 Australians will suffer from AD, with associated health costs of about 3% of the GDP. AD is characterized by two major brain lesions, beta-amyloid plaques and neurofibrillary tangles (NFTs). The latter contain a protein called tau which is in a fibrillar and highly phosphorylated state. We were the first to establish a transgenic animal model of pre-tangles and, together with Dr. Hutton's laboratory, of NFT formation. We could further show that injections of beta-amyloid into brains of our tau mutant mice enhanced the NFT pathology in these mice. By Functional Genomics we identied genes and proteins, which are induced by tau expression. The specific aim of this proposal is to determine whether oxidative stress enhances the tau pathology in our tau mutant mice and whether distinct brain areas are particularly susceptible to this kind of stress. The reason for addressing this question is twofold: On the one hand, we have found in our mice that reactive oxygen species are increased, secondly it is known that some brain areas in the AD brain are degenerating, whereas others are not. A second aim is to develop novel tau transgenic models where individual interactions of tau with cellular proteins are disturbed. Finally, we want to determine whether the two kinases BMX and FAK and the phosphatase PPV regulate tau phosphorylation in vivo. Together, we hope that our efforts lead to a better understanding of the pathogenic mechanisms in AD and related disorders. As pathocascades are likely to be shared between a range of diseases, these findings may also contribute to other fields of research, such as Parkinson's disease. Ultimately, these efforts will assist in the development of a safe treatment of AD.Read moreRead less