α-Synuclein facilitates the toxicity of oxidized catechol metabolites:: Implications for selective neurodegeneration in Parkinson's disease
α-Synuclein facilitates the toxicity of oxidized catechol metabolites:: Implications for selective neurodegeneration in Parkinson's disease
复制标题
DOI：
10.1016/j.febslet.2006.03.018
复制
发表时间：
2006-04-03
期刊：
影响因子：
3.5
通讯作者：
Itoyama, Y
中科院分区：
文献类型：
--
作者：
Hasegawa, T;Matsuzaki-Kobayashi, M;Itoyama, Y
自由基，包括多巴胺（DA）的氧化代谢产物，长期以来一直涉及帕金森病（PD）的发病机制。然而，这种氧化应激和α-突触核蛋白（α-S），路易体的主要成分之间的关系，仍然未知。在这项研究中，我们建立了组成型表达α-S和四环素调节酪氨酸酶的神经元细胞。虽然酪氨酸酶过表达诱导细胞凋亡，但野生型或A53 T突变体人α-S与酪氨酸酶的共表达进一步加剧了细胞死亡。在此过程中，证明了α-S寡聚体的形成和线粒体膜电位的降低。该细胞模型可能重建突触核蛋白病中α-S的病理代谢，并为探索PD中黑质变性的可能病理机制提供有用的工具。(c)2006年欧洲生物化学学会联合会。Elsevier B. V.出版，保留所有权利。
Free radicals, including dopamine (DA)-oxidized metabolites, have long been implicated in pathogenesis of Parkinson's disease (PD). However, the relationships between such oxidative stresses and alpha-synuclein (alpha-S), a major constituent of Lewy bodies, remain unknown. In this study, we established neuronal cells that constitutively express alpha-S and tetracycline-regulated tyrosinase. While tyrosinase overexpression induced apoptosis, co-expression of wild type or A53T mutant human alpha-S with tyrosinase further exacerbated cell death. In this process, the formation of alpha-S oligomers and the reduction in mitochondrial membrane potential were demonstrated. This cellular model may reconstitute the pathological metabolism of alpha-S in the synucleinopathy and provide a useful tool to explore possible pathomechanisms of nigral degeneration in PD. (c) 2006 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.