Ko L, Mehta N D, Farrer M, Easson C, Hussey J, Yen S, Hardy J, Yen S H
Department of Pharmacology, Mayo Clinic, Jacksonville, Florida 32224, USA.
J Neurochem. 2000 Dec;75(6):2546-54. doi: 10.1046/j.1471-4159.2000.0752546.x.
Linkage of alpha-synuclein (alpha-SN) mutations to familial Parkinson's disease (PD) and presence of alpha-SN as a major constituent of Lewy body in both sporadic and familial PD implicate alpha-SN abnormality in PD pathogenesis. Here we demonstrate that overexpression of wild-type or mutant alpha-SN does not cause any deleterious effect on the growth or continued propagation of transfected human cells, but overproduction of mutant alpha-SN heightens their sensitivity to menadione-induced oxidative injury. Such enhanced vulnerability is more pronounced in neuronal transfectants than in their nonneuronal counterparts and is associated with increased production of reactive oxygen species. The data suggest that mutated alpha-SN, especially with an alanine-to-proline substitution at residue 30, sensitizes neuronal cells to oxidative damage.
α-突触核蛋白（α-SN）突变与家族性帕金森病（PD）相关联，并且α-SN作为散发性和家族性PD中路易小体的主要成分，这表明α-SN异常参与了PD的发病机制。在此我们证明，野生型或突变型α-SN的过表达对转染的人细胞的生长或持续增殖不会造成任何有害影响，但突变型α-SN的过量产生会增强其对甲萘醌诱导的氧化损伤的敏感性。这种增强的易损性在神经元转染细胞中比在非神经元转染细胞中更明显，并且与活性氧的产生增加有关。数据表明，突变的α-SN，尤其是在第30位残基处由丙氨酸替换为脯氨酸的突变体，使神经元细胞对氧化损伤敏感。
