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
Central Nervous System Dendritic Cells – Guilty Or Not Guilty?
Funder
National Health and Medical Research Council
Funding Amount
$481,594.00
Summary
The central nervous system although structurally and functionally unique, must be able to mount protective immunological responses. However, breakdown in local and central immunoregulatory processes can lead to clinically disabling inflammatory conditions such as uveitis and multiple sclerosis. This project will investigate the role of Dendritic cells in models of autoimmune diseases affecting the eye and brain. The data will greatly aid our ability to design new immunotherapies to treat these b ....The central nervous system although structurally and functionally unique, must be able to mount protective immunological responses. However, breakdown in local and central immunoregulatory processes can lead to clinically disabling inflammatory conditions such as uveitis and multiple sclerosis. This project will investigate the role of Dendritic cells in models of autoimmune diseases affecting the eye and brain. The data will greatly aid our ability to design new immunotherapies to treat these blinding and crippling diseases.Read moreRead less
Novel Pathomechanisms And Therapeutic Targets In Neurodegenerative Diseases
Funder
National Health and Medical Research Council
Funding Amount
$340,038.00
Summary
This fellowship will provide new insight into the molecular processes underlying onset and progression of common brain conditions, including Alzheimer’s disease, frontotemporal dementia and motor neuron disease. Furthermore, new therapeutic targets for these diseases will be developed and tested in model systems, to facilitate future translation into clinical application, and to overcome the lack of treatments.
New Projection Neurons Are Added To The Brain Throughout Life – Identifying Their Source And Function.
Funder
National Health and Medical Research Council
Funding Amount
$505,991.00
Summary
Scientists aim to use our body’s own stem cells to make new nerve cells for brain repair. There are two major types of nerve cell: long range and short range; and until now we did not know how to make new long range nerves. I recently discovered that a special type of brain stem cell, the OPC, makes new long range nerves throughout life. We are building on this discovery by trying to understand the signals that control this process in order to direct OPCs towards nerve regeneration.
Myelin Remodelling: A Novel Form Of Neural Plasticity
Funder
National Health and Medical Research Council
Funding Amount
$605,849.00
Summary
Myelin is the insulation of the central nervous system (CNS). We have demonstrated that CNS insulation is not fixed. It changes throughout life. This project aims to find out why this happens. In particular we will investigate the role of dynamic insulation in learning and memory, and examine the role of nervous system activity in promoting the addition of new insulation. This research will provide valuable insight into multiple sclerosis, Alzheimer's dementia and mental health disorders.
Mapping The Neural Circuits Involved In Appetite And Feeding Behaviour
Funder
National Health and Medical Research Council
Funding Amount
$404,892.00
Summary
My research project involves deconstructing the neural circuitry underlying feeding behaviour using innovative genetically-based methods. I aim to identify and characterise the major projections of the oxytocin-expressing neurons in the paraventricular hypothalamic nucleus, which have recently been identified as critical in the feeding neurocircuitry. This emerging field of research is predicted to transform our understanding and treatment of disorders such as obesity and anorexia nervosa.
Site-specific Tau Phosphorylation To Treat And Understand Alzheimer’s Disease
Funder
National Health and Medical Research Council
Funding Amount
$943,902.00
Summary
Alzheimer’s disease (AD) is the most common form of dementia. Unfortunately, current therapies are ineffective. Our laboratory has made an important contribution to understanding the events that lead to brain cell malfunction in AD. I recently found a novel concept that changes the view of AD completely. In the next 3 years, I aim to develop therapeutic tools based on this novel concept and find out more about how it can protect brains from AD.
Novel Pathomechanisms And Therapeutic Approaches In Alzheimer's Disease And Related Dementias
Funder
National Health and Medical Research Council
Funding Amount
$804,106.00
Summary
Currently, over 200,000 Australians are affected by Alzheimer's disease (AD) or frontotemporal lobar degeneration (FTLD), causing a huge socio-economic damage. To overcome the lack of effective treatments, we need to understand the underlying causes and translate them into therapy. Using state-of-the-art cell culture and genetic mouse models, I will reveal fundamental processes in AD and related dementias, and develop tailored treatments to battle these devastating disorders.
Alzheimer’s disease is a progressive brain disease which is results in memory loss and brain cell death. All currently prescribed drugs treat the memory loss but are unable to stop the deterioration of brain cells. We have previously developed a class of drugs that reverse memory loss targeting – these drugs target a protein called IRAP. We recently found that these drugs also reduce the disease pathology. This research proposal aims to investigate the role of IRAP in the initiation or progressi ....Alzheimer’s disease is a progressive brain disease which is results in memory loss and brain cell death. All currently prescribed drugs treat the memory loss but are unable to stop the deterioration of brain cells. We have previously developed a class of drugs that reverse memory loss targeting – these drugs target a protein called IRAP. We recently found that these drugs also reduce the disease pathology. This research proposal aims to investigate the role of IRAP in the initiation or progression of Alzheimer’s disease pathology.Read moreRead less