IDENTIFICATION AND FUNCTION OF RECEPTORS ON SYMPATHETIC TERMINAL SCHWANN CELLS
Funder
National Health and Medical Research Council
Funding Amount
$235,500.00
Summary
The terminals of sympathetic nerves control many of the internal organs. Pharmacological intervention to promote or antagonize the effects of these terminals is very important in a number of different disease states of the autonomic nervous system. The present research proposal sets out to determine the way in which glial cells that partly envelop these terminals control their capacity to function.
Proteolytic Cleavage Of The P75 Neurotrophin Receptor Mediates Cell Death
Funder
National Health and Medical Research Council
Funding Amount
$238,500.00
Summary
The p75 neutrotophin receptor (p75NTR) is a major inducer of nerve cell death, and is active in a wide range of neurodegenerative conditions, including Alzheimer's disease, motor neuron disease, multiple sclerosis, stroke and nerve trauma. This study aims to understand and to characterise the events that regulate this receptor. In particular, we will investigate the role that cleavage or controlled breakdown of the receptor plays in mediating its cell death activity. A fundamental aspect of this ....The p75 neutrotophin receptor (p75NTR) is a major inducer of nerve cell death, and is active in a wide range of neurodegenerative conditions, including Alzheimer's disease, motor neuron disease, multiple sclerosis, stroke and nerve trauma. This study aims to understand and to characterise the events that regulate this receptor. In particular, we will investigate the role that cleavage or controlled breakdown of the receptor plays in mediating its cell death activity. A fundamental aspect of this proposal is determining whether cleavage is due to presenilin-dependent activity, given that presenilin mutations have been demonstrated in most familial Alzheimer s disease cases. While this will increase our understanding of one of factors contributing to Alzheimer's disease, it also has much broader implications. A wide range of pharmaceuticals which regulate presenilin cleavage are already being developed and clinically tested for their efficacy in the treatment of Alzheimer s disease. Should our research demonstrate that p75NTR cleavage is the key process that regulates neuronal degeneration it will have major ramifications for approaches to the treatment of other p75NTR-associated neurodegenerative conditions.Read moreRead less
Deciphering How PTEN Phosphatase Mediates Excitotoxic Neuronal Death
Funder
National Health and Medical Research Council
Funding Amount
$519,715.00
Summary
In stroke patients, oxygen deprivation indirectly induces massive nerve cell death by activating a cell death-promoting enzyme called PTEN. We aim at unravelling (i) how PTEN is activated by oxygen deprivation, (ii) where the activated PTEN is localised in cells, and (iii) how the activated and optimally localised PTEN induces nerve cell death. The study will benefit development of therapeutic strategies to protect against brain damage in stroke.
Identification And Origin Of Neuronal Precursors In The Adult Mouse Hippocampus
Funder
National Health and Medical Research Council
Funding Amount
$284,250.00
Summary
It is now clear that new neurons continue to be generated under normal conditions in at least 2 regions of the adult mammalian brain: the olfactory bulb (smell centre) and the hippocampus (organ responsible for memory and learning). These new neurons replace those lost as part of aging and, as such, are vital to normal brain function. Recently, these results have been extended to show that various insults, such as stroke, can cause the proliferation of precursor cells in the adult brain, which u ....It is now clear that new neurons continue to be generated under normal conditions in at least 2 regions of the adult mammalian brain: the olfactory bulb (smell centre) and the hippocampus (organ responsible for memory and learning). These new neurons replace those lost as part of aging and, as such, are vital to normal brain function. Recently, these results have been extended to show that various insults, such as stroke, can cause the proliferation of precursor cells in the adult brain, which ultimately results in the addition of new nerve cells that go on to repair the pathological damage. Although the production of new nerve cells under normal conditions and following damage is highly significant, we still know surprisingly little about the nature of the precursor population which produces these cells and even less about their regulation. For the most part, this has been due to our inability to identify and isolate the brain stem cell. Thus, over the last 5 years I have adapted cell sorting techniques - which are normally used to separate blood cells to isolate populations of cells from the brains of adult mice. As a result of my work, we are now in the position to sort for a population of stem cells that are known to give rise to new brain cells in the adult olfactory bulb. This work will be extended to identify and characterise the precursor population that resides in the hippocampus. The identification of this hippocampal precursor population will thus provide the foundation for developing new approaches for the treatment of diseases such as strokeRead moreRead less