...
  • 主题
高级搜索  >
历史搜索 清空历史
首页> 外文期刊>Neurochemistry International: The International Journal for the Rapid Publication of Critical Reviews, Preliminary and Original Research Communications in Neurochemistry >alpha-Synuclein enhances secretion and toxicity of amyloid beta peptides in PC12 cells.
【24h】

alpha-Synuclein enhances secretion and toxicity of amyloid beta peptides in PC12 cells.

机译：α-突触核蛋白可增强PC12细胞中淀粉样β肽的分泌和毒性。

获取原文
获取原文并翻译 | 示例
           
页面导航
  • 摘要
  • 著录项
  • 相似文献
  • 相关主题

摘要

alpha-Synuclein is the fundamental component of Lewy bodies which occur in the brain of 60% of sporadic and familial Alzheimer's disease patients. Moreover, a proteolytic fragment of alpha-synuclein, the so-called non-amyloid component of Alzheimer's disease amyloid, was found to be an integral part of Alzheimer's dementia related plaques. However, the role of alpha-synuclein in pathomechanism of Alzheimer's disease remains elusive. In particular, the relationship between alpha-synuclein and amyloid beta is unknown. In the present study we showed the involvement of alpha-synuclein in amyloid beta secretion and in the mechanism of amyloid beta evoked mitochondria dysfunction and cell death. Rat pheochromocytoma PC12 cells transfected with amyloid beta precursor protein bearing Swedish double mutation (APPsw) and control PC12 cells transfected with empty vector were used in this study. alpha-Synuclein (10microM) was found to increase by twofold amyloid beta secretion from control and APPsw PC12 cells. Moreover, alpha-synuclein decreased the viability of PC12 cells by about 50% and potentiated amyloid beta toxicity leading to mitochondrial dysfunction and caspase-dependent programmed cell death. Inhibitor of caspase-3 (Z-DEVD-FMK, 100microM), and a mitochondrial permeability transition pore blocker, cyclosporine A (2microM) protected PC12 cells against alpha-synuclein or amyloid beta evoked cell death. In contrast Z-DEVD-FMK and cyclosporine A were ineffective in APPsw cells containing elevated amount of amyloid beta treated with alpha-synuclein. It was found that the inhibition of neuronal and inducible nitric oxide synthase reversed the toxic effect of alpha-synuclein in control but not in APPsw cells. Our results indicate that alpha-synuclein enhances the release and toxicity of amyloid beta leading to nitric oxide mediated irreversible mitochondria dysfunction and caspase-dependent programmed cell death.
机译：α-突触核蛋白是路易体的基本成分，它发生在60％的散发性和家族性阿尔茨海默氏病患者的大脑中。此外，发现阿尔茨海默氏病淀粉样蛋白的所谓非淀粉样成分α-突触核蛋白的蛋白水解片段是阿尔茨海默氏症痴呆相关斑块的组成部分。然而，α-突触核蛋白在阿尔茨海默氏病的发病机制中的作用仍然难以捉摸。特别地，α-突触核蛋白和淀粉样β之间的关系是未知的。在本研究中，我们显示了α-突触核蛋白参与淀粉样蛋白β分泌以及淀粉样蛋白β诱发线粒体功能障碍和细胞死亡的机制。本研究使用的大鼠嗜铬细胞瘤PC12细胞被带有瑞典双突变（APPsw）的淀粉样β前体蛋白转染，而对照组被空载体转染了PC12细胞。发现α-突触核蛋白（10microM）通过对照和APPsw PC12细胞的两倍淀粉样β分泌增加。此外，α-突触核蛋白将PC12细胞的活力降低了约50％，并且增强了淀粉样β的毒性，导致线粒体功能障碍和caspase依赖性程序性细胞死亡。 caspase-3抑制剂（Z-DEVD-FMK，100microM）和线粒体通透性过渡孔阻滞剂，环孢菌素A（2microM）保护PC12细胞免受α-突触核蛋白或淀粉样β引起的细胞死亡。相反，Z-DEVD-FMK和环孢菌素A在APPsw细胞中无效，该细胞包含用α-突触核蛋白处理过的淀粉样β量升高的蛋白质。发现神经元和诱导型一氧化氮合酶的抑制逆转了α-突触核蛋白在对照中而不是在APPsw细胞中的毒性作用。我们的结果表明，α-突触核蛋白增强了淀粉样β的释放和毒性，导致一氧化氮介导的不可逆线粒体功能障碍和caspase依赖性程序性细胞死亡。

著录项

相似文献

  • 外文文献
  • 中文文献
  • 专利
获取原文

客服邮箱：kefu@zhangqiaokeyan.com

京公网安备：11010802029741号 ICP备案号：京ICP备15016152号-6 六维联合信息科技 (北京) 有限公司©版权所有

  • 客服微信

  • 服务号