自噬-溶酶体途径和泛素-蛋白酶体系统在肌萎缩侧索硬化发病中的作用

摘要

肌萎缩侧索硬化(ALS)是常见的成人运动神经元疾病.迄今为止,ALS的病因及发病机制尚未完全明确,但是越来越多的证据表明蛋白的错误折叠和清除障碍参与了包括ALS在内的多种神经变性疾病的发生与进展.自噬-溶酶体途径(ALP)和泛素-蛋白酶体系统(UPS)是机体修复或消除异常蛋白质的两种最主要的途径,在神经变性疾病中发挥着重要作用.两者都参与细胞的分化、发育和凋亡,贯穿于细胞生长发育和病理生理过程,任何一种系统受损都会导致细胞功能障碍甚至死亡.本文主要对自噬和UPS在ALS发病中的作用予以综述.%Amyotrophiclateralsclerosis(ALS)isthemostcommonadult-onsetmotorneurondisease.AlthoughtheetiologyandpathomechanismunderlyingALSremainobscuresofar,thereisincreasingevidencethatmisfoldedorimpairedeellularproteinsisinvolvedinthepathogenesisofvariousneurodegenerativediseases,includingALS.Autophagy-lysosomepathway(ALP)andubiquitin-proteasomesystem(UPS)arethetwomajorsystemsfordegradationofaberrantproteins,whichplayanimportantpartinneurodegenerativediseases.Bothofthemtakepartinthedifferentiation,maturationandapoptosisofcells.Neitheroftheminjuredcancausethedeteriorationofvariouscellularfunctions,evenleadtoneuronalcelldeath.Thisreviewmainlydiscussedtheroleofmacroautophagyandubiquitin-proteasomesysteminALS.