The Inhibition of Neurotransmitter Release by Alpha-synuclein

Although current therapy manages the symptoms of Parkinson's disease, we still understand very little about the underlying mechanism of degeneration, and hence have no treatment that addresses the eventual disease progression.

Recent work has shown that the protein alpha-synuclein has a central role in the development of Parkinson's disease. However, the mechanism by which synuclein contributes to degeneration remains entirely unknown. Synuclein localizes to the nerve terminal, suggesting a role in neurotransmitter release at the synapse, but previous work has not yielded conclusive evidence about its physiological role. We have now identified a clear effect of alpha-synuclein on the normal function of the nerve terminal, and will use this as an entry point to understand the physiological role of this protein. Since simple overexpression of alpha-synuclein appears sufficient to cause PD, the results have direct relevance for neural degeneration.