蛋白降解途径与帕金森病关系研究进展.pdfVIP

中国临床神经科学 2011年第 19卷第1期 Chin J Clin Neurosci 2011,9 (11) ,83~89 83 进 展 蛋白降解途径与帕金森病关系研究进展 侯玲玲，王 涛 (华中科技大学同济医学院附属协和医院神经内科430022) 关键词　泛素蛋白酶体系统；自噬溶酶体途径；帕金森病 摘要 帕金森病(PD) 中具病理诊断意义的蛋白包涵体路易小体的出现提示蛋白聚集异常或清除障碍在PD 发病中的作 用。泛素蛋白酶体系统(UP S)和自噬溶酶体途径(ALP)是细胞内两个主要的蛋白质降解通路。随着对UPS 在PD 发病机 制中作用的认识加深，ALP 与PD 的关系也越来越受关注，一系列应用ALP 增强剂的研究显示，通过增强自噬、增加 异常蛋白的清除，具有良好的PD 治疗前景。近来的研究发现，ALP 和UPS 在功能上相互联系，如何合理调节自噬及 有效利用ALP 与UP S 之间的联系，由此精确调控细胞内蛋白质的代谢还有待进一步研究。 Progress in Role of Protein Degradation System in Pathogenesis of Parkinson ’s Disease H OU Ling- Ling ，WANG Tao Department of Neurology, Union Hospital, Tongj i Medical College, Huazhong University of Science and Technology, Wuhan 430022, China KEY WORDS ubiquitin-proteasome system; autophagy-lysosome pathway ；Parkinson ’s disease ABSTRACT The presence of Lewy body, a central pathological finding associated with Parkinson ’s disease (PD) implicates the essential role of dysregulated or impaired protein degradation function in this disease. The two maj or intracellular protein degradation systems are the ubiquitin-proteasome system (UPS) and the autophagy-lysosome pathway (ALP). While the UPS has been extensively researched, much attention has been payed to the role of ALP in PD. Increasing evidence has shown that up-regulated autophagy by autophagy enhancers evidently promoted the degradation of protein aggregates, which may be a prospective therapy for PD by inducing autophagy. Furthermore, recent studies have revealed the interaction between ALP and UPS, much exploration on utilizing the link between these two degradation systems effectively, in order to maintain or restore the normal degrading function under various pathological conditions are warranted. 帕金森病(Parkinson ’s disease ，PD)是中老年人群 存争议，但异常蛋白聚集增多或清除障碍，导致神经元 常见的中枢神经系统变性疾病。迄今为止，P