Tau磷酸化及其激酶在缺氧缺血性脑损伤中的作用机制研究进展  

Research progress on the mechanisms of Tau phosphorylation and its kinases in hypoxic-ischemic brain damage

作　　者：黄麒屹 向优 唐佳航 陈力嘉 李坤霖 赵威芳 王茜 HUANG Qi-Yi;XIANG You;TANG Jia-Hang;CHEN Li-Jia;LI Kun-Lin;ZHAOWei-Fang;WANG Qian(Department of Pathology and Pathophysiology,School of Basic Medical Sciences,Kunming Medical University,Kunming 650500,China)

机构地区：[1]昆明医科大学基础医学院病理与病理生理学系,昆明650500

出　　处：《生理学报》2025年第1期139-150,共12页Acta Physiologica Sinica

基　　金：National Natural Science Foundation of China(No.81860278);Basic Research Project of Science and Technology Department of Yunnan Province,China(No.202201AT070197)。

摘　　要：缺氧缺血性脑损伤(hypoxic-ischemic brain damage,HIBD)是导致中老年人残疾和新生儿高致残率、低生存率及长期身体功能缺陷的主要原因之一。HIBD主要病理表现为神经元损伤和髓鞘丢失。Tau蛋白是脑内重要的微管相关蛋白,存在于神经元和少突胶质细胞中,可调节多种细胞活动,如细胞分化成熟、轴突转运和维持细胞骨架结构。磷酸化是Tau的一种常见的化学修饰,在生理状态下,其参与调节Tau结构和功能,维持正常细胞骨架和生物学功能;在病理状态下,Tau磷酸化发生异常,使其结构改变并影响其功能,致Tau病(Tauopathy)发生。研究发现,脑缺氧缺血可使Tau磷酸化发生异常变化,参与HIBD的病理过程。同时,脑缺氧缺血可诱导氧化应激和炎症,多个具有调控Tau磷酸化作用的Tau蛋白激酶在此过程中被激活,并且Tau磷酸化异常与它们激活有关。因此,探索HIBD激活Tau蛋白激酶的具体分子机制,以及阐明它们与Tau异常磷酸化之间的关系,这对未来开展HIBD相关治疗的研究具有重要意义。本综述重点关注Tau磷酸化在HIBD中的作用机制,以及Tau蛋白激酶与Tau磷酸化之间的潜在关系,为HIBD的干预和治疗提供依据。Hypoxic-ischemic brain damage(HIBD)is one of the main causes of disability in middle-aged and elderly people,as well as high mortality rates and longterm physical impairments in newborns.The pathological manifestations of HIBD include neuronal damage and loss of myelin sheaths.Tau protein is an important microtubule-associated protein in brain,exist in neurons and oligodendrocytes,and regulates various cellular activities such as cell differentiation and maturation,axonal transport,and maintenance of cellular cytoskeleton structure.Phosphorylation is a common chemical modification of Tau.In physiological condition,it maintains normal cell cytoskeleton and biological functions by regulating Tau structure and function.In pathological conditions,it leads to abnormal Tau phosphorylation,influence its structure and functions,resulting in Tauopathies.Studies have shown that brain hypoxia-ischemia could cause abnormal alteration in Tau phosphorylation,then participating in the pathological process of HIBD.Meanwhile,brain hypoxia-ischemia can induce oxidative stress and inflammation,and multiple Tau protein kinases are activated and involved in Tau abnormal phosphorylation.Therefore,exploring specific molecular mechanisms by which HIBD activates Tau protein kinases,and elucidating their relationship with abnormal Tau phosphorylation are crucial for future researches on HIBD related treatments.This review aims to focus on the mechanisms of the role of Tau phosphorylation in HIBD,and the potential relationships between Tau protein kinases and Tau phosphorylation,providing a basis for intervention and treatment of HIBD.

关 键 词：TAU 缺氧缺血性脑损伤 Tau蛋白激酶 FYN GSK3Β CDK5 MAPK PKA 

分 类 号：R72[医药卫生—儿科]