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
Suppressor Of Cytokine Signalling-2 (SOCS2) And Its Role In Neuronal Development And Function
Funder
National Health and Medical Research Council
Funding Amount
$451,980.00
Summary
Injury to the brain or spinal cord at present often results in permanent damage, such as paralysis, which is largely due to a failure of neurons to regrow at the injury site. In order to overcome this, we are trying to find ways of making new neurons grow, either from stem cells present in the nervous system or transplanted from cells grown in tissue culture. However, little is known about how a neural stem cell decides to become a neuron or another cell type, such as a glial cell and so we are ....Injury to the brain or spinal cord at present often results in permanent damage, such as paralysis, which is largely due to a failure of neurons to regrow at the injury site. In order to overcome this, we are trying to find ways of making new neurons grow, either from stem cells present in the nervous system or transplanted from cells grown in tissue culture. However, little is known about how a neural stem cell decides to become a neuron or another cell type, such as a glial cell and so we are examining factors which influence this process, which is called differentiation. Growth factors are important mediators of this process and suppressor of cytokine signalling (SOCS) proteins are important in determining how cells respond to growth factors. The overall aims of this project are to determine the role that SOCS genes and in particular, SOCS2 play in neural stem cell differentiation into neurons and glia, neuron process outgrowth and neuronal and glial injury responses in the nervous system. This will be examined in normal cells and cells which over-express or do not express SOCS2 genes. Understanding the biology of neural growth factor responsiveness may eventually allow us to devise therapeutic strategies for use following brain-spinal injury or disease, including generation of neurons from stem cells.Read moreRead less
Regulation Of Brain Development By Members Of The Fibroblast Growth Factor Family
Funder
National Health and Medical Research Council
Funding Amount
$65,685.00
Summary
The brain is the most complex organ in the body. It is made up of many different types of cells broadly classified into two classes called neurons and glia. The growth of the brain from a small population of immature neuroepithelial cells to many different types of neurons and glia is controlled by small potent proteins called growth factors. We understand that many different families of growth factors are involved in the development of the brain but not how they do what they do. We are studying ....The brain is the most complex organ in the body. It is made up of many different types of cells broadly classified into two classes called neurons and glia. The growth of the brain from a small population of immature neuroepithelial cells to many different types of neurons and glia is controlled by small potent proteins called growth factors. We understand that many different families of growth factors are involved in the development of the brain but not how they do what they do. We are studying the members of one particular family known as the Fibroblast Growth Factor family or FGFs. We want to find out how they instruct young brain cells to grow and divide and turn into mature neurons.Read moreRead less