The proteins associated with the neurotrophin retrograde transport signalling endosome

Funded Activity Summary

According to estimates taken from the Australian Bureau of Statistics population projection series, during the next forty years the incidence of Alzheimer's disease or a related dementia in Australia is predicted to increase by 254%. One of the key issues in neurobiology is to understand the mechanisms regulating the survival of nerve cells. Nerve Growth Factor (NGF) acts to cause nerve cell survival by being transported from the target tissue to the cell body in a discrete organelle described as the Signalling Endosome. This process is termed Retrograde Axonal Transport. The signalling endosome is assembled in the nerve terminal and also contains proteins normally activated by NGF known as Second Messengers. Neurodegenerative diseases, such as Alzheimer's disease, occur due to the death of nerve cells and a disturbance of the retrograde axonal transport of NGF may contribute to this death. NGF has been shown to have clinical potential as it can promote neuronal repair and survival after injury. However clinical trials have demonstrated an unacceptable toxicity for this protein. Therefore, another approach taken to produce the restorative benefits of NGF is to stimulate second messenger pathways downstream from the NGF receptor. This approach could provide important new therapeutic potentials as we can target more selective components of these survival pathways and have a greater chance to find less toxic drugs. This project will identify the second messengers normally accompanying NGF from the nerve terminal which promote nerve cell survival. We will describe the way these proteins are recruited to the signalling endosome. Survival of nerve cells requires the activation of these proteins and we shall determine where this occurs. Understanding the molecular basis for the delivery of the retrograde survival signal in neurons is vital if new therapeutic strategies for the treatment of neurodegenerative disease and traumatic nerve damage are to be developed.

Funded Activity Details

Start Date: 01-01-2005

End Date: 01-01-2007

Funding Scheme: NHMRC Project Grants

Funding Amount: $243,000.00

Funder: National Health and Medical Research Council

Research Topics

ANZSRC Field of Research (FoR)

ANZSRC Socio-Economic Objective (SEO)

There are no SEO codes available for this funding activity

Other Keywords

Cell signalling | Down Syndrome | Endosome | Nerve regeneration | Nervous system regeneration | Neurodegenerative diseases | Neurotrophins | Receptor Trafficking | Retrograde axonal transport | Tauopathies

Related Links