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A Novel Intracellular Roadblock To Cobalamin Utilization In Ageing And Alzheimer�s Disease
Funder
National Health and Medical Research Council
Funding Amount
$11,304.00
Summary
Vitamin B12 is required for red blood cell formation, DNA synthesis and normal neurological function. B12 deficiency contributes to age-related cognitive decline and Alzheimer�s disease. This research will provide important new information regarding the ageing process and the impact that brain changes associated with ageing and Alzheimer's disease have on B12 metabolism. It will provide important information related to the therapeutic potential of B12.
Defining The Function Of Apolipoprotein-D In Alzheimer's Disease
Funder
National Health and Medical Research Council
Funding Amount
$457,231.00
Summary
Alzheimer's disease (AD) prevalence is rising and there is no curative treatment. Neurotoxic amyloid-beta peptide and concomitant lipid oxidation in the brain contribute to the cause of AD. We have identified a new pathway by which a protein called apoD may inhibit lipid oxidation in the AD brain. We will test the impact that changing apoD levels in neurons and in genetically modified mice has on neuron stress and AD-like characteristics. This may reveal new avenues to prevent or treat AD.
There are escalating numbers of Alzheimer�s disease sufferers. This Project aims to provide a better understanding of the fundamental process underlying the damage to brain circuitry in this condition. This proposal may provide key information regarding the relationship between the major pathological changes of Alzheimer�s disease, identifying the cellular mechanisms that are crucial to this process, and providing new avenues for therapeutic agents targeted at the earliest stage of AD.
Structure-function Studies Of Insulin-regulated Membrane Aminopeptidase
Funder
National Health and Medical Research Council
Funding Amount
$526,702.00
Summary
Memory loss can occur as a result of injuries or disease such as Alzheimer's disease, the fourth biggest killer in developed countries. Currently there is no effective treatment for memory loss. This proposal concerns the biochemical investigation of a protein involved in memory and possibly diabetes. This work is expected to provide an understanding of how this protein functions in the body and will form the basis for the design of drugs for the treatment of memory loss.
Copper Homeostasis And APP-induced Neurodegeneration In Drosophila
Funder
National Health and Medical Research Council
Funding Amount
$381,223.00
Summary
Alzheimer s disease, a debilitating neurodegenerative disorder suffered by many of our elderly, is characterised by the presence of abnormal protein accumulations called plaques in the brains of affected patients. Plaques contain amyloid protein and also have high levels of the essential metals copper and zinc. Copper is needed for the formation of these protein aggregations and increases the toxic effects of amyloid, leading to the idea that copper-binding chemicals could be used to treat Alzhe ....Alzheimer s disease, a debilitating neurodegenerative disorder suffered by many of our elderly, is characterised by the presence of abnormal protein accumulations called plaques in the brains of affected patients. Plaques contain amyloid protein and also have high levels of the essential metals copper and zinc. Copper is needed for the formation of these protein aggregations and increases the toxic effects of amyloid, leading to the idea that copper-binding chemicals could be used to treat Alzheimer s disease. However experiments in animal models have produced conflicting results, some suggesting that increased copper levels protect against neuronal damage while others claim the opposite effect. Comparison of these studies is hampered by the different experimental systems used. We will clarify the role of copper in the progression of Alzheimer s disease using a simple insect model, the fly Drosophila melanogaster. Production of amyloid in Drosophila neuronal tissues produces a neurodegenerative effect similar to that seen in human brains, but in a matter of weeks rather than the years required in humans. We will combine production of amyloid with production of copper uptake and export proteins to investigate the effect of changing copper levels. We will also test the effect of increasing copper and other metals in the diet to see whether dietary levels are an important factor in disease progression. Finally, we will use the Drosophila model to test large numbers of metal binding compounds and drugs for ones that slow or halt the neuronal damage caused by amyloid production, identifying potential therapeutics for the treatment of Alzheimer s disease. This work will provide a vital and definitive clarification of the role of copper in the progression of Alzheimer s disease and potentially lead to the development of novel treatments for this disease that is rapidly becoming a major social and economic problem in the developed world.Read moreRead less
Investigation Of Dysfunction Of SIGMAR1 In Transgenic Mouse Models, A Novel Gene Implicated In Neurodegeneration
Funder
National Health and Medical Research Council
Funding Amount
$492,119.00
Summary
At present, there are no effective therapies for frontotemporal dementia or motor neuron disease. We have identified the SIGMAR1 gene as having a crucial role for these diseases. More importantly, there are therapeutically relevant small molecule drugs that are known to modulate the activity of this gene. We aim to determine the efficacy of pharmacological modulation of Sigma-1 receptor activity in mouse models of dementia.
A new scan called PiB PET shows the build up of amyloid protein deposits in the brain in all patients with Alzheimer's disease (AD) but also in 30% of normal elderly persons. This study will track the build up of amyloid and clinical progress in 280 elderly Australians to confirm that this scan can detect AD before symptoms and investigate factors that influence this build up and its damaging effects on memory and thinking. Early detection of Alzheimer's disease will assist accurate diagnosis an ....A new scan called PiB PET shows the build up of amyloid protein deposits in the brain in all patients with Alzheimer's disease (AD) but also in 30% of normal elderly persons. This study will track the build up of amyloid and clinical progress in 280 elderly Australians to confirm that this scan can detect AD before symptoms and investigate factors that influence this build up and its damaging effects on memory and thinking. Early detection of Alzheimer's disease will assist accurate diagnosis and the development of treatment.Read moreRead less
Targeting Tau Phosphorylation To Treat And Prevent Acquired Epilepsy, Neurodegeneration And Neuropsychiatric Disease Following A Brain Injury
Funder
National Health and Medical Research Council
Funding Amount
$524,820.00
Summary
This project will explore a new approach to the prevention and treatment of epilepsy and the associated mental health disorders following a brain injury. This involves inhibiting pathological forms of the Tau protein, which has been implicated in the development of epilepsy and neurodegeneration. The drug that will be tested in this study has already been demonstrated to be safe and well tolerated in humans, meaning that a positive result from these studies could be expediently translated into c ....This project will explore a new approach to the prevention and treatment of epilepsy and the associated mental health disorders following a brain injury. This involves inhibiting pathological forms of the Tau protein, which has been implicated in the development of epilepsy and neurodegeneration. The drug that will be tested in this study has already been demonstrated to be safe and well tolerated in humans, meaning that a positive result from these studies could be expediently translated into clinical studies.Read moreRead less
Alzheimer's disease is the most common form of dementia and is the fourth biggest killer in developed countries. This proposal concerns the biochemical investigation of a protein implicated in Alzheimer's disease. This work is expected to lead to the determination of the three-dimensional shape of the protein which will provide an understanding of what the protein's normal function is in the body and may form the basis for the design of drugs to combat the disease.
Intracellular Trafficking Of Copper And Platinum-based Chemotherapuetics
Funder
National Health and Medical Research Council
Funding Amount
$268,328.00
Summary
Platinum-based anti cancer drugs such as Cisplatin are effective against a number of cancers of the head, colon, lungs and ovaries. Tumour resistance to these drugs has been closely associated with changes in genes that control the movement of copper in and out of cells. We hypothesize that the same genes regulate distribution of both copper and Cisplatin. By investigating these pathways, we aim to find ways to predict and prevent tumour resistance to this important anti cancer treatment.