alpha-synuclein metabolism in human neurodegenerative disease

Funded Activity Summary

Alpha-synuclein is an abundant brain protein of unknown function. Gene mutations have been linked to rare cases with inherited Parkinson s disease. Now this protein is believed to play an important role in all forms of Parkinson s disease, Lewy body dementia, and multiple system atrophy. These diseases are designated as synucleinopathies to emphasize the potential importance of alpha-synuclein in these disease. Recent studies suggest alpha-synuclein may also contribute to many other human diseases, including Alzheimer s disease. The reason how and why alpha-synuclein is involved in so many human neurological diseases is not clear. We recently discovered that alpha-synuclein in normal human brain exists in multiple form of N-terminal fragments, presumably generated through certain endogenous enzymes. These cleaved products are markedly increased in Parkinson s disease. Studies by other groups suggest alpha-synuclein and fragments may be released to the cerebrospinal fluids. Based on these findings, we hypothesize that alpha-synuclein is modified by specific enzymes in neurons and released. This is probably a normal alpha-synuclein metabolic pathway whose homeostasis may be, for reasons yet to be understood, altered in synucleinopathies. Similar mechanism may be also involved in other common diseases in which the protein is believed to play a role. This project aims to elucidate the potential role of alpha-synuclein metabolism in Parkinson s and related diseases by examining alpha-synuclein metabolites in the brains affected by these diseases. Results from this grant will provide new information about alpha-synuclein metabolism in neurons, new insights into the mechanistic involvement of alpha-synuclein in these neurodegenerative diseases. Antibody reagents generated from this study may be valuable in neuropathological and clinical assessment of changes in synucleinopathies.

Funded Activity Details

Start Date: 01-01-2002

End Date: 01-01-2004

Funding Scheme: NHMRC Project Grants

Funding Amount: $381,430.00

Funder: National Health and Medical Research Council

Research Topics

ANZSRC Field of Research (FoR)

Neurology And Neuromuscular Diseases

ANZSRC Socio-Economic Objective (SEO)

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Other Keywords

Lewy body | Parkinson's disease | ageing disease | alpha-synuclein | dementia with Lewy bodies | monoclonal antibody | neurochemistry | neuronal degeneration | protein metabolism

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