蛋白降解途径与帕金森病关系研究进展

Progress in Role of Protein Degradation System in Pathogenesis of Parkinson's Disease

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(UPS)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UPS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。

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 major 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.