摘要
3-磷酸甘油醛脱氢酶(GAPDH)是一种经典的糖酵解蛋白,除了行使糖酵解功能外,还参与多种细胞生理功能。研究显示,GAPDH酶蛋白与帕金森病(PD)相关蛋白如α-突触核蛋白等有相互作用,参与Lewy小体形成,介导多种因素诱导的神经元细胞凋亡。gapdh基因过表达、GAPDH酶蛋白异常聚集和核转位与PD的发生有关。GAPDH在应激条件下发生巯基亚硝基化,巯基亚硝基化的GAPDH(SNO-GAPDH)通过与Siah1结合发生核转位,介导凋亡级联反应。司来吉兰及其结构类似物通过与GAPDH酶蛋白结合,干扰凋亡信号通路,发挥神经保护作用。GOSPEL(GAPDH's competitor of siah protein enhances life)是一种新发现的GAPDH酶蛋白神经毒性通路中的负调节蛋白,可能为PD治疗提供新的靶点。
Glyceraldehyde-3-phosphate dehydrogenase（GAPDH） is a classic glycolytic protein,it is not only a simple housekeeping gene or an internal control protein,but also has multiple physiological functions.Previous studies showed that GAPDH interacted with Parkinson＇s disease（PD）-associated proteins,such as a-synuclein,and involved in the formation of Lewy body,and mediated neurons apoptosis under stresses.Overexpression,abnormal aggregation and nuclear translocation of GAPDH induced by oxidative or nitrosative stress were putatively associated with PD.Experiments indicated that stresses induced nitric oxide formation,leading to S-nitrosylation of GAPDH（SNO-GAPDH） that binded to Siah1 and translocated into the nucleus and thereby initiated apoptotic cascades.Deprenyl and other propargylamines show neuroprotective effect by binding to GAPDH,interfering apoptotic signal pathway.GOSPEL（GAPDH＇s competitor of siah protein enhances life） is identified as a novel,negative regulator of the GAPDH neurotoxic pathway,which may be a new target for PD therapy.
出处
《中国临床神经科学》
2011年第5期539-543,共5页
Chinese Journal of Clinical Neurosciences
基金
国家自然科学基金资助项目(编号:30870866)
国家自然科学基金资助项目(编号:81071021)
武汉市科技局重点攻关计划(编号:20066002100)
关键词
3-磷酸甘油醛脱氢酶
帕金森病
凋亡
神经变性疾病
glyceraldehyde-3-phosphate dehydrogenase
Parkinson＇s disease
apoptosis
neurodegenerative disease
