摘要
微管相关蛋白tau(Microtubule-associated protein tau,tau)的过度磷酸化是阿尔茨海默病(Alzheimer’s disease,AD)脑内的主要病理变化之一。研究证实,tau蛋白的过度磷酸化出现在AD的早期阶段,并且认为抑制tau蛋白过度磷酸化是AD治疗的关键。然而,tau蛋白过度磷酸化及其磷酸化后的聚集机制尚不完全清楚。重要的是,大量研究表明,蛋白磷酸酶2A(protein phosphatase 2A,PP2A)活性的降低在tau蛋白过度磷酸化的形成中发挥至关重要的作用。因此,我们综述了PP2A功能紊乱和tau蛋白病理,重点阐述了PP2A功能紊乱在tau蛋白过度磷酸化中的作用。此外,改善PP2A功能紊乱可成为AD治疗的一个策略。
One of the principal pathological features of the progression of Alzheimer’s disease(AD)is the occurrence of aberrant phosphorylation of the microtubule-associated protein tau(tau)in the AD brain.Moreover,it has been reported that abnormal hyperphosphorylation of tau protein is an early manifestation of AD and inhibition of tau protein phosphorylation is thought to be the key of AD therapy.However,the evolving mechanisms by which tau protein is hyperphosphorylated and accumulated are still not clear.Most importantly,the down-regulation of protein phosphatase 2 A(PP2 A)activity is thought to play an important role in the formation of tau protein hyperphosphorylation.Here,this review focuses on recent developments of tau protein hyperphosphorylation mainly involving in PP2 A dysfunction.We also highlight that the evolving mechanism of PP2 A dysfunction by which tau protein is hyperphosphorylated and contributes to its accumulation is reshaping the framework for the development of therapeutics targeting PP2 A to treat AD.
作者
燕飞
黄南渠
金凤
Yan Fei;Huang Nanqu;Jin Feng(Key Laboratory of Basic Pharmacology and Joint International Research Laboratory of Ethnomedicine of Ministry of Education,Zunyi Medical University,Zunyi Guizhou 563099,China;Department of Drug Clinical Trial of The Third Affiliated Hospital of Zunyi Medical University,Zunyi Guizhou 563000,China)
出处
《合肥医科大学学报》
2020年第3期390-404,共15页
Journal of Zunyi Medical University
基金
国家自然科学基金资助项目(NO:81660599)
合肥医科大学大学生创新训练项目(NO:ZYDC2018005,NO:ZYDC2019070)。
