Disruption of Protein Quality Control in Parkinson's Disease
Disruption of Protein Quality Control in Parkinson's Disease
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DOI：
10.1101/cshperspect.a009423
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发表时间：
2012-05-01
影响因子：
5.4
通讯作者：
Petrucelli, Leonard
中科院分区：
文献类型：
--
作者：
Cook, Casey;Stetler, Caroline;Petrucelli, Leonard
帕金森病（Parkinson's disease，PD）与许多与衰老相关的神经退行性疾病一样，其特征在于蛋白质在特定神经元亚群中的异常积累。尽管研究人员最近阐明了PD的遗传原因，但关于导致疾病中蛋白质沉积增加的原因仍有很多未知之处。鉴于蛋白质聚集增加不仅可能是由于产量增加，也可能是由于蛋白质清除率降低，因此必须研究这两种可能性作为潜在的PD罪魁祸首。本文综述了蛋白质清除的调节系统，包括泛素蛋白酶体系统（UPS）和自噬-溶酶体途径。文献暗示失败的这些机制，如UPS功能障碍导致的环境毒素和突变的α-突触核蛋白和parkin，以及macroautophagic通路故障，因为氧化应激和老化的发病机制PD也进行了讨论。
Parkinson's disease (PD), like a number of neurodegenerative diseases associated with aging, is characterized by the abnormal accumulation of protein in a specific subset of neurons. Although researchers have recently elucidated the genetic causes of PD, much remains unknown about what causes increased protein deposition in the disease. Given that increased protein aggregation may result not only from an increase in production, but also from decreased protein clearance, it is imperative to investigate both possibilities as potential PD culprits. This article provides a review of the systems that regulate protein clearance, including the ubiquitin proteasome system (UPS) and the autophagy-lysosomal pathway. Literature implicating failure of these mechanisms-such as UPS dysfunction resulting from environmental toxins and mutations in alpha-synuclein and parkin, as well as macroautophagic pathway failure because of oxidative stress and aging-in the pathogenesis of PD is also discussed.