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The Cystine Glutamate Antiporter And Classical Glutamate Transporters In Normal And Pathological Brains And Retinae
Funder
National Health and Medical Research Council
Funding Amount
$416,000.00
Summary
This project will examine the role of a system that transports a toxic neurotransmitter, glutamate out of cells where it is relatively harmless, into the space surrounding nerve cells where it can be highly toxic. Previous models for the aberrant release of glutamate under pathological conditions such as strokes, have relied on the notion that other specialised glutamate transporters which normally work to remove glutamate from the space surrounding nerve cells, actually reverse their direction ....This project will examine the role of a system that transports a toxic neurotransmitter, glutamate out of cells where it is relatively harmless, into the space surrounding nerve cells where it can be highly toxic. Previous models for the aberrant release of glutamate under pathological conditions such as strokes, have relied on the notion that other specialised glutamate transporters which normally work to remove glutamate from the space surrounding nerve cells, actually reverse their direction of action and release glutamate. The current study investigates a transport system (called the cystine-glutamate antiporter) where the normal direction of action is to release glutamate. This system has been overlooked despite evidence that it could be involved in releasing glutamate and thus contribute to the death of nerve cells in a variety of human pathologies including glaucoma of the eye, epilepsy, and brain damage that occurs when the blood supply to the brain is interrupted, such as after a heart attack. This study examines both human tissues and animal models of disease states to determine if similar transport systems are present and if the cystine-glutamate antiporter might contribute to human nervous diseases. The function and distribution of the cystine-glutamate antiporter will be compared with classical transporters, under normal and pathological conditions, including situations where we have shown that it is possible to experimentally perturb normal glutamate transporter expression.Read moreRead less
Astrocytic Glutamate Transporters: Molecular Characteristics Of Their Activity-dependent Localization And Targeting
Funder
National Health and Medical Research Council
Funding Amount
$558,189.00
Summary
Dysfunction of glutamate transport is implicated in the pathology of neurodegenerative conditions. Our aim is to understand how the molecules responsible for glutamate transport are organized on the cell surface and how their movement within cells regulates transporter activity. Advances of this type will indicate new pharmacological and molecular biological strategies for the management of brain disorders.
Glutamate is one of the major neurotransmitters in the brain. It plays a very important role in most brain functions such as the ability to learn and the development of memory, but the lack of control of glutamate concentrations in the brain also underlies many pathological changes that cause neurological disorders such Alzheimer's disease, disability following a stroke, motor neurone disease and Parkinson's disease. These diseases place an enormous social and economic burden on society and in o ....Glutamate is one of the major neurotransmitters in the brain. It plays a very important role in most brain functions such as the ability to learn and the development of memory, but the lack of control of glutamate concentrations in the brain also underlies many pathological changes that cause neurological disorders such Alzheimer's disease, disability following a stroke, motor neurone disease and Parkinson's disease. These diseases place an enormous social and economic burden on society and in order to better understand and treat these diseases it is important to understand some of the fundamental biochemical processes that underlie both normal and pathogical functions of the key neurotransmitter glutamate. This project will investigate how the concentrations of glutamate are tightly regulated to maintain normal brain function and also to avoid the potentially pathological consequences when these control mechanisms fail.Read moreRead less
Modulating Retinal Glutamate Transport In Health And Disease
Funder
National Health and Medical Research Council
Funding Amount
$256,527.00
Summary
Damage can occur to nervous tissues like the retina and brain when there is a reduction in the blood supply. This can occur as a result of a blood clot, stroke or the eye disease, glaucoma. These conditions often result in blindness. Much of the neuronal damage is due to the release of an excess of glutamate. Glutamate is a chemical (neurotransmitter) that nerves use to communicate with each other, but it is toxic to nerves when present at high concentrations. This project will investigate the m ....Damage can occur to nervous tissues like the retina and brain when there is a reduction in the blood supply. This can occur as a result of a blood clot, stroke or the eye disease, glaucoma. These conditions often result in blindness. Much of the neuronal damage is due to the release of an excess of glutamate. Glutamate is a chemical (neurotransmitter) that nerves use to communicate with each other, but it is toxic to nerves when present at high concentrations. This project will investigate the mechanisms that regulate the concentration of glutamate in the retina. If these mechanisms could be made to work more efficiently, they may prevent the build-up of the glutamate and therefore prevent damage to the nerve cells. Understanding these mechanisms will aid in the development of an effective treatment to prevent blindness when there is a blockage of the blood supply to the retina.Read moreRead less