脑卒中(cerebral stroke)是由脑动脉出血或梗塞引起的急性脑血管病，约80％的脑卒中临床 病例为缺血性脑卒中。自噬流障碍是导致神经元缺血性损伤的重要致病因素，而如何改善自噬流障碍从而减轻缺血性脑损伤的策略仍需深入探究。研究表明，转录因子EB(transcription factor EB，TFEB)是自噬-溶酶体信号通路的关键调节分子。TFEB的活性由其磷酸化水平决定，磷酸化的TFEB通过与14-3-3黏附蛋白结合存留于胞质，当其去磷酸化后则快速向核内转位，进而上调"协同溶酶体表达与调控(coordinated lysosomal expression and regulation，CLEAR)"信号，促进溶酶体生成及自噬相关基因转录，从而增强自噬流。本文重点就TFEB核转位改善缺血性脑卒中神经元自噬流障碍的分子机制进行详细阐述，旨在为脑卒中治疗及脑缺血病理研究提供参考。
The Molecular Mechanism of Nuclear Translocation of Transcription Factor EB in the Improvement of Neuronal Autophagic Flux Dysfunction after Ischemic Stroke
Cerebral stroke is an acute cerebrovascular disease caused by cerebral artery hemorrhage or infarction.About 80％of the clinical cases of stroke are ischemic stroke.Autophagic flux dysfunction is an important pathogenic factor leading to neuronal ischemic injury.And strategies to improve the reduction of autophagic flux disorder to reduce ischemic brain injury still need to be further explored.Studies have shown that transcription factor EB(TFEB)is a key regulator of autophagy-lysosomal signaling pathway.The activity of TFEB is determined by its phosphorylation level.The phosphorylated TFEB is retained in the cytoplasm by binding to the 14-3-3 adhesion protein.When it is dephosphorylated,it rapidly translo-cates into the nucleus,and then up-regulates the'coordinated lysosomal expression and regulation(CLEAR)'signal to promote lysosomal production and autophagy-related gene transcription,thereby en-hancing autophagic flux.This article focuses on the molecular mechanism of TFEB nuclear translocation to improving autophagic flux dysfunction in ischemic stroke neurons,which may help to provide reference for stroke treatment and pathological study of cerebral ischemia.
万方数据
维普
