Proteolytic cleavage of the p75 neurotrophin receptor mediates cell death

Funded Activity 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 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.

Funded Activity Details

Start Date: 01-01-2004

End Date: 01-01-2006

Funding Scheme: NHMRC Project Grants

Funding Amount: $238,500.00

Funder: National Health and Medical Research Council

Research Topics

ANZSRC Field of Research (FoR)

Medical parasitology

ANZSRC Socio-Economic Objective (SEO)

There are no SEO codes available for this funding activity

Other Keywords

Alzheimer's disease | Stroke | cell death/ apoptosis | metalloprotease | nerve trauma | neurodegenerative disease | p75 neurotrophin receptor | presenilin | signalling

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