脑缺血/再灌注损伤后泛素化蛋白质修饰的研究进展

Research progress in ubiquitinated protein modification after cerebral ischemia/reperfusion injury

泛素-蛋白酶体途径介导的翻译后修饰是机体调节蛋白质水平与功能的重要机制,在调控细胞稳态和存活等过程中发挥重要作用。脑缺血/再灌注损伤(cerebral ischemia/reperfusion injury,CI/RI)过程中蛋白质翻译后修饰尤为重要,缺血易损区泛素-蛋白酶体系统(ubiquitin proteasome system,UPS)结构及功能异常,最终导致迟发性神经元凋亡。深入探究CI/RI后泛素化蛋白质修饰有助于开发治疗新策略、研发新药物。文章就UPS在CI/RI模型、谷氨酸兴奋性毒性和脑缺血耐受中的作用及机制进行简要总结,同时探讨蛋白酶体调节剂的脑保护作用,有望为深入探究CI/RI后泛素化蛋白质修饰调节机制提供新思路。

Post-translational modification mediated by the ubiquitin proteasome pathway is an important mechanism for organisms to regulate protein levels and functions,which plays an important role in regulating cell homeostasis and survival.Protein post-translational modification is particularly important in cerebral ischemia/reperfusion injury(CI/RI).The structure and function of the ubiquitin proteasome system(UPS)in the area are vulnerable to ischemia,which would eventually lead to delayed apoptotic neuronal death.In-depth exploration of the mechanism of ubiquitinated protein modification after CI/RI will help to develop new therapeutic strategies and drugs.This review aims to briefly summarize the role and mechanism of the UPS in CI/RI models,glutamate excitotoxicity,and cerebral ischemic tolerance.We also discuss the brain protective effects of proteasome modulators in this review.All of views are expected to inspire new ideas for further exploration of the regulatory mechanism of ubiquitinated protein modification after CI/RI.