Lim Kah-Leong
National Neuroscience Institute, Neurodegeneration Research Laboratory & Parkinson's Disease & Movement Disorders Center, 11 Jalan Tan Tock Seng, 308433, Singapore.
Expert Rev Proteomics. 2007 Dec;4(6):769-81. doi: 10.1586/14789450.4.6.769.
Parkinson's disease (PD) is the most common neurodegenerative movement disorder. Although a subject of intense research, the etiology of PD remains poorly understood. Over the last decade, the ubiquitin-proteasome system (UPS) has emerged as a compelling player in PD pathogenesis. Disruption of the UPS, which normally identifies and degrades intracellular proteins, is thought to promote the toxic accumulation of proteins detrimental to neuronal survival, thereby contributing to their demise. Support for this came from a broad range of studies, including genetics, gene profiling and post-mortem analysis, as well as in vitro and in vivo modeling. Notably, various cellular and animal models of PD based on direct disruption of UPS function reproduce the salient features of PD. However, several gaps remain in our current knowledge regarding the precise role of UPS dysfunction in the pathogenesis of the disease. Current thoughts regarding their relationship are reviewed here and some major unresolved questions, the clarification of which would considerably advance our understanding of the implicated role of the UPS in PD pathogenesis, are discussed.
帕金森病（PD）是最常见的神经退行性运动障碍。尽管是深入研究的课题，但PD的病因仍知之甚少。在过去十年中，泛素-蛋白酶体系统（UPS）已成为PD发病机制中一个引人注目的因素。正常情况下识别并降解细胞内蛋白质的UPS功能紊乱，被认为会促进对神经元存活有害的蛋白质的毒性积累，从而导致神经元死亡。包括遗传学、基因谱分析和尸检分析以及体外和体内模型研究在内的广泛研究都支持了这一点。值得注意的是，基于直接破坏UPS功能的各种PD细胞和动物模型再现了PD的显著特征。然而，关于UPS功能障碍在该疾病发病机制中的确切作用，我们目前的知识仍存在一些空白。本文综述了关于它们关系的当前观点，并讨论了一些主要的未解决问题，对这些问题的澄清将大大推进我们对UPS在PD发病机制中所涉作用的理解。
