Alpha Synuclein, cellular dysfunction and Parkinson disease

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Alpha-synuclein was the first gene identified for Parkinsons disease and has been associated with a number of detrimental effects in cells and in animal models. The protein itself is expressed at high levels in neurons where it is associated with membranous structures including presynaptic vesicles. One difficult question is why a-synuclein would, at least in some circumstances, lead to the death of neurons. One possibility is that aspects of neurotransmitter metabolism are important and we have previously shown that some groups of neurons are more susceptible than others to a-synuclein toxicity. Dopaminergic cells are especially vulnerable and we have recently reported that increasing expression of a-synuclein makes human neuroblastoma cells more susceptible to dopamine associated toxicity. Ongoing work in the lab is aimed at understanding the normal and toxic functions of a-synuclein.