α-突触核蛋白的多巴胺依赖性神经毒性：帕金森病中选择性神经变性的一种机制。
Dopamine-dependent neurotoxicity of alpha-synuclein: a mechanism for selective neurodegeneration in Parkinson disease.
作者信息
Xu Jin, Kao Shyan-Yuan, Lee Frank J S, Song Weihong, Jin Lee-Way, Yankner Bruce A
机构信息
Department of Neurology, Harvard Medical School and Division of Neuroscience,The Children's Hospital, Boston, Massachusetts, USA.
出版信息
Nat Med. 2002 Jun;8(6):600-6. doi: 10.1038/nm0602-600.
The mechanism by which dopaminergic neurons are selectively lost in Parkinson disease (PD) is unknown. Here we show that accumulation of alpha-synuclein in cultured human dopaminergic neurons results in apoptosis that requires endogenous dopamine production and is mediated by reactive oxygen species. In contrast, alpha-synuclein is not toxic in non-dopaminergic human cortical neurons, but rather exhibits neuroprotective activity. Dopamine-dependent neurotoxicity is mediated by 54 83-kD soluble protein complexes that contain alpha-synuclein and 14-3-3 protein, which are elevated selectively in the substantia nigra in PD. Thus, accumulation of soluble alpha-synuclein protein complexes can render endogenous dopamine toxic, suggesting a potential mechanism for the selectivity of neuronal loss in PD.
多巴胺能神经元在帕金森病（PD）中选择性丧失的机制尚不清楚。我们在此表明，培养的人多巴胺能神经元中α-突触核蛋白的积累会导致细胞凋亡，这种凋亡需要内源性多巴胺的产生，并由活性氧介导。相比之下，α-突触核蛋白在非多巴胺能人皮质神经元中没有毒性，反而表现出神经保护活性。多巴胺依赖性神经毒性由包含α-突触核蛋白和14-3-3蛋白的54 83-kD可溶性蛋白复合物介导，这些复合物在PD患者的黑质中选择性升高。因此，可溶性α-突触核蛋白蛋白复合物的积累可使内源性多巴胺具有毒性，这提示了PD中神经元丧失选择性的潜在机制。
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