α-synuclein promotes mitochondrial deficit and oxidative stress
α-synuclein promotes mitochondrial deficit and oxidative stress
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DOI：
10.1016/s0002-9440(10)64553-1
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发表时间：
2000-08-01
影响因子：
6
通讯作者：
Masliah, E
中科院分区：
文献类型：
--
作者：
Hsu, LJ;Sagara, Y;Masliah, E
突触前蛋白α-突触核蛋白的异常积累最近被认为与阿尔茨海默病和帕金森病的发病机制有关。由于这些条件下的神经变性可能与线粒体功能障碍和氧化应激相关，因此在下丘脑神经元细胞中研究了α-突触核蛋白的作用。行（GT 1 -7）。在这些细胞中α-突触核蛋白过表达导致α-突触核蛋白免疫阳性包涵体样结构的形成和线粒体改变，伴随着自由基水平的增加和促性腺激素释放激素分泌的减少。这些改变通过用抗氧化剂如维生素E预处理而得到改善。总之，这些结果表明，α-突触核蛋白的异常积累可能导致线粒体改变，这可能导致氧化应激，并最终导致细胞死亡。
Abnormal accumulation of the presynaptic protein alpha-synuclein has recently been implicated in the pathogenesis of Alzheimer's and Parkinson's diseases. Because neurodegeneration in these conditions might be associated with mitochondrial dysfunction and oxidative stress, the effects of alpha-synuclein were investigated in a hypothalamic neuronal cell. line (GT1-7). alpha-Synuclein overexpression in these cells resulted in formation of alpha-synuclein-immunopositive inclusion-like structures and mitochondrial alterations accompanied by increased levels of free radicals and decreased secretion of gonadotropin-releasing hormone. These alterations were ameliorated by pretreatment with anti-oxidants such as vitamin E. Taken together these results suggest that abnormal accumulation of alpha-synuclein could lead to mitochondrial alterations that may result In oxidative stress and, eventually, cell death.