GSK-3β及其抑制剂在缺血性卒中的研究进展  

Research progress of GSK-3βand its inhibitors in ischemic stroke

作　　者：陈文文 程一峰 李婷婷[1] 方馨妍 杨春瑛 CHEN Wen-Wen;CHENG Yi-Feng;LI Ting-Ting;FANG Xin-Yan;YANG Chun-Ying(Health Science Center,Ningbo University,Ningbo 315211,China;The First Affiliated Hospital of Ningbo University,Ningbo 315000,China)

机构地区：[1]宁波大学医学部,宁波315211 [2]宁波大学附属第一医院,宁波315000

出　　处：《生命科学》2025年第3期313-320,共8页Chinese Bulletin of Life Sciences

基　　金：宁波市科技计划项目(202003N4243);浙江省医药卫生科技计划(一般项目)(2025KY1310)。

摘　　要：缺血性卒中往往导致严重的神经功能缺损,对人民群众的生命财产安全造成极大的损害。糖原合成酶激酶-3β(glycogen synthase kinase-3β,GSK-3β)是一种丝氨酸/苏氨酸蛋白激酶,在脑缺血过程中,GSK-3β参与磷脂酰肌醇-3-激酶(phosphatidylinositol 3-kinase,PI3K)/蛋白激酶B(protein kinase B,AKT)、Wnt、Notch、核因子红细胞2相关因子2(nuclear factor erythroid 2-related factor 2,Nrf2)等信号通路,通过调控氧化应激、神经炎症来加重脑缺血损伤,恶化中风结局。因此,抑制GSK-3β被认为是预防和治疗缺血性卒中的潜在策略,而相应的GSK-3β抑制剂在临床前研究中的有效结果似乎都提示了其作为脑卒中补充治疗方案的可行性。本综述讨论了GSK-3β的结构以及在缺血性卒中中调控的信号通路,并介绍了目前在脑血管疾病中研究的几种GSK-3β抑制剂,以期为缺血性卒中治疗新方法提供参考。Ischemic stroke often results in serious neurological deficits,causing great damage to the safety of people's lives and property.Glycogen synthase kinase-3β(GSK-3β)is a serine/threonine protein kinase,which is involved in phosphatidylinositol 3-kinase(PI3K)/protein kinase B(AKT),Wnt,Notch,and nuclear factor erythroid 2-related factor 2(Nrf2)signaling pathways,and can aggravate cerebral ischemic injury and worsen stroke outcomes by participating in oxidative stress and neuroinflammation.Therefore,GSK-3βinhibition is considered as a potential strategy for the prevention and treatment of ischemic stroke,and its promising results in preclinical studies point to its feasibility as an adjunctive therapy for stroke.This review discusses the structure of GSK-3β,the signaling pathways involved in ischemic stroke,and introduces the current research of several GSK-3βinhibitors in cerebrovascular diseases,which provides a reference for new approaches in the treatment of ischemic stroke.

关 键 词：GSK-3Β 缺血性卒中 PI3K/AKT WNT/Β-CATENIN NRF2 NF-ΚB 

分 类 号：R743.3[医药卫生—神经病学与精神病学]