Alpha Synuclein, cellular dysfunction and Parkinson disease

α -突触核蛋白是第一个被确定为帕金森病的基因，在细胞和动物模型中与许多有害影响有关。该蛋白本身在神经元中高水平表达，与包括突触前囊泡在内的膜结构有关。一个难题是，至少在某些情况下，为什么a-突触核蛋白会导致神经元死亡。一种可能性是神经递质代谢的各个方面是重要的，我们之前已经表明，一些神经元组比其他神经元组更容易受到a-突触核蛋白毒性的影响。多巴胺能细胞尤其脆弱，我们最近报道了a-突触核蛋白表达的增加使人类神经母细胞瘤细胞更容易受到多巴胺相关毒性的影响。实验室正在进行的工作旨在了解a-突触核蛋白的正常和毒性功能。

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.