...
  • 主题
高级搜索  >
历史搜索 清空历史
首页> 外文期刊>Journal of Neurochemistry: Offical Journal of the International Society for Neurochemistry >The contribution of alpha synuclein to neuronal survival and function - Implications for Parkinson's disease
【24h】

The contribution of alpha synuclein to neuronal survival and function - Implications for Parkinson's disease

机译：α突触核蛋白对神经元存活和功能的贡献-对帕金森氏病的意义

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

The aggregation of alpha synuclein (-syn) is a neuropathological feature that defines a spectrum of disorders collectively termed synucleinopathies, and of these, Parkinson's disease (PD) is arguably the best characterized. Aggregated -syn is the primary component of Lewy bodies, the defining pathological feature of PD, while mutations or multiplications in the -syn gene result in familial PD. The high correlation between -syn burden and PD has led to the hypothesis that -syn aggregation produces toxicity through a gain-of-function mechanism. However, -syn has been implicated to function in a diverse range of essential cellular processes such as the regulation of neurotransmission and response to cellular stress. As such, an alternative hypothesis with equal explanatory power is that the aggregation of -syn results in toxicity because of a toxic loss of necessary -syn function, following sequestration of functional forms -syn into insoluble protein aggregates. Within this review, we will provide an overview of the literature linking -syn to PD and the knowledge gained from current -syn-based animal models of PD. We will then interpret these data from the viewpoint of the -syn loss-of-function hypothesis and provide a potential mechanistic model by which loss of -syn function could result in at least some of the neurodegeneration observed in PD. By providing an alternative perspective on the etiopathogenesis of PD and synucleinopathies, this may reveal alternative avenues of research in order to identify potential novel therapeutic targets for disease modifying strategies.
机译：α突触核蛋白（-syn）的聚集是一种神经病理学特征，定义了一系列疾病，统称为突触核病，其中帕金森氏病（PD）可以说是最好的特征。聚集的-syn是路易小体的主要成分，是PD的明确病理特征，而-syn基因的突变或繁殖会导致家族性PD。 -syn负担与PD之间的高度相关性导致了这样一个假说，即-syn聚集通过功能获得机制产生毒性。然而，-syn被暗示在多种必需的细胞过程中起作用，例如神经传递的调节和对细胞应激的反应。这样，具有相同解释力的另一种假设是-syn的聚集会导致毒性，因为在将功能形式-syn隔离为不溶的蛋白质聚集体后，必需的-syn功能会发生毒性损失。在这篇综述中，我们将概述-syn与PD的相关文献以及从当前基于-syn的PD动物模型中获得的知识。然后，我们将从-syn功能丧失假说的角度解释这些数据，并提供一种潜在的机制模型，通过该模型，-syn功能丧失可能导致PD中观察到的至少一些神经变性。通过提供有关PD和突触核蛋白病的致病机理的另一种观点，这可能揭示出另一种研究途径，以便确定潜在的新疾病治疗策略的靶标。

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