Trace Element Regulation In Neurological Disease: From Molecular Pathogenesis To Translational Impact.
Funder
National Health and Medical Research Council
Funding Amount
$631,370.00
Summary
Neurodegenerative diseases such as dementia and motor neuron disease are a major health burden for Australia and new approaches to treatment are urgently required. Essential trace elements such as copper, zinc and iron show major changes in neurodegneration, however, we do not understand how this drives disease processes. This proposal will develop an innovative 3D ‘brain on a chip’ cell model to probe the role of trace elements in brain pathology and identify exciting new treatments options.
Functional Copper Deficiency Models Of Alzheimer's Disease
Funder
National Health and Medical Research Council
Funding Amount
$454,691.00
Summary
Alzheimer's disease is a serious neurodegenerative disease which increases in incidence with age. It affects the quality of life and care required for approximately 160,000 Australians and costs the national economy 6.6 billion dollars per annum. Current therapy is of limited efficacy. Our studies are directed towards testing the hypothesis that a functional deficiency of the essential trace element, copper, occurs in the brain with ageing, and this leads to oxidative stress and death of neurons ....Alzheimer's disease is a serious neurodegenerative disease which increases in incidence with age. It affects the quality of life and care required for approximately 160,000 Australians and costs the national economy 6.6 billion dollars per annum. Current therapy is of limited efficacy. Our studies are directed towards testing the hypothesis that a functional deficiency of the essential trace element, copper, occurs in the brain with ageing, and this leads to oxidative stress and death of neurons associated with Alzheimer's disease. We will use animal and cell culture models to test this hypothesis which is based on promising preliminary data from such models. We believe that beta amyloid, which accumulates in Alzheimer's brains and is believed to be a major part of the pathological mechanism, has a normal role in maintaining copper balance and that this balance is disturbed by ageing or particular mutations. This research should lead to better treatments using drugs which mobilise copper entry into cells.Read moreRead less
Studies On Mechanisms Of Vesicular Trafficking And Catalysis For The Menkes (MNK) Copper-transporting P-type ATPase
Funder
National Health and Medical Research Council
Funding Amount
$363,757.00
Summary
Copper is an essential trace element for all organisms. Copper is needed for many processes including energy metabolism, the making and maintenance of strong bones and arteries with sufficient elasticity, the synthesis of chemical transmitters in the brain and for the reactions which remove toxic Ofree radicalsO. Copper is also used by the proteins involved in important neurological diseases including Alzheimers disease and Omad cowO disease. Menkes disease is an inherited and usually lethal cop ....Copper is an essential trace element for all organisms. Copper is needed for many processes including energy metabolism, the making and maintenance of strong bones and arteries with sufficient elasticity, the synthesis of chemical transmitters in the brain and for the reactions which remove toxic Ofree radicalsO. Copper is also used by the proteins involved in important neurological diseases including Alzheimers disease and Omad cowO disease. Menkes disease is an inherited and usually lethal copper deficiency disorder in humans, and the diverse and detrimental symptoms of this disease related to organs and tissues described above is a stark indicator of the essentiality of copper. We have carried out extensive research on Menkes disease and in particular the Menkes protein which in normal individuals plays a major role in maintaining the copper balance in cells, i.e. enough Cu to satisfy nutritional needs of cells but not too much which causes toxicity. The normal Menkes protein catalyses the transport of Cu across membranes of cells to the areas where it is needed by copper-dependent enzymes which themselves catalyse important chemical reactions. The normal Menkes protein functions as a molecular pump. We have discovered that this protein can OsenseO Cu concentrations in the cell and when these reach potentially toxic levels it can move (traffick) via small vesicles to the plasma membrane which surrounds cells. There it pumps the excess Cu out of the cell and returns to its original location. Our studies are directed to understanding the molecular mechanisms which permit this remarkable protein to achieve a copper balance in living cells. The findings will be of major significance in understanding and treating acquired and inherited diseases involving copper deficiency or copper toxicity.Read moreRead less
Element Labeling Antibodies For Bio-imaging Of Proteins: A Case Study Of Beta-amyloid In Alzheimer's Disease Mouse Models
Funder
National Health and Medical Research Council
Funding Amount
$221,136.00
Summary
This project will develop new analytical methods for quantitative in-situ imaging of beta-amyloid in mouse brains. Beta-amyloid deposition in the brain is associated with Alzheimer�s disease. It is also planned to simultaneously image metal ions, which are also implicated in the deposition of beta-amyloid. Application of these novel methods to Alzheimer�s disease mouse models will provide new knowledge and significant insights into the aetiology of Alzheimer�s disease by determining the relation ....This project will develop new analytical methods for quantitative in-situ imaging of beta-amyloid in mouse brains. Beta-amyloid deposition in the brain is associated with Alzheimer�s disease. It is also planned to simultaneously image metal ions, which are also implicated in the deposition of beta-amyloid. Application of these novel methods to Alzheimer�s disease mouse models will provide new knowledge and significant insights into the aetiology of Alzheimer�s disease by determining the relationship between amyloid proteins and metal ions.Read moreRead less
Linkage Infrastructure, Equipment And Facilities - Grant ID: LE100100115
Funder
Australian Research Council
Funding Amount
$350,000.00
Summary
High-temperature probes for investigating phase transitions and reaction kinetics in thin films, nanostructured materials and biomaterials. This infrastructure for high temperature surface analysis and in-situ diagnostics as a function of temperature and gas environments will enhance Australia's capabilities in creating new materials for devices that will meet needs in medical, communications, environmental and security applications. The facility will enable researchers to understand and exploi ....High-temperature probes for investigating phase transitions and reaction kinetics in thin films, nanostructured materials and biomaterials. This infrastructure for high temperature surface analysis and in-situ diagnostics as a function of temperature and gas environments will enhance Australia's capabilities in creating new materials for devices that will meet needs in medical, communications, environmental and security applications. The facility will enable researchers to understand and exploit interfacial phenomena and to tailor processing-microstructure-composition correlations, so as to design new materials with the best performance possible. Probes with unique capabilities will measure surface morphology, optical properties, elemental composition and crystallographic phase.The facility will be the first in Australia to offer a comprehensive study of structure and properties at high temperature.Read moreRead less
Investigating The Iron Proteome In Alzheimer’s Disease
Funder
National Health and Medical Research Council
Funding Amount
$514,644.00
Summary
Iron is essential for brain function. When the delicate balance of metals in the brain is disturbed, neurodegenerative effects such as those seen in Alzheimer’s disease are observed. Although we know there is a link between iron and Alzheimer’s disease, we do not know which specific iron proteins are involved. This project will provide the first characterisation of different iron proteins in the brain to understand the mechanisms of disease and help in the search for new treatments.