Modulation of Neurotrophin Receptor Signaling: understanding the determinants and phenotypic consequences. [ 2006 - 2008 ]

Research Grant

Researchers: Dr Simon Murray (Principal investigator)

Brief description Peripheral nerves are complex structures consisting of motor and sensory neurons, their axons, and the cells that support them, Schwann cells. Peripheral neuropathy is a common neurological problem which covers many disorders of the peripheral nervous system. There are predominately two types of neuropathies: those where there is a primary loss or degeneration of neurons and-or their axons; and those where the Schwann cells are lost. These degenerative pathologies have prompted interest in the potential of growth factors as a general therapy for peripheral neuropathy. The neurotrophins are a family of neuronal growth factors that influence many key aspects of neuronal development, as well as the maintenance of the mature peripheral nervous system. Work in cells in vitro and in animal models provides solid support for the hypothesis that the neurotrophins prevent neuronal death. However clinical trials testing the neurotrophins has led to variable results and side effects due to their many effects. To make these therapies useful, it is crucial to expand our knowledge about how they actually work and which of the many responses they induce actually produces their beneficial effect. This project aims to achieve this goal. I have identified a mechanism where neurotrophin signaling is selectively modulated in vitro. The aims of this project are to understand how this modulation of neurotrophin signaling is mediated, to identify the cellular substrates that are selectively activated and to determine what the biological consequences of this modulation are. Only through analyses such as these can we gain new insights into neurotrophin signaling and develop an understanding of how the activities of neurotrophins can be more precisely harnessed to generate new and more productive therapeutic approaches.

Funding Amount $AUD 507,270.54

Funding Scheme NHMRC Project Grants

Notes Standard Project Grant