以哺乳动物雷帕霉素靶蛋白为靶点治疗阿尔茨海默病的研究进展

Research progress on the treatment of Alzheimer's disease based on the target of mammalian target of rapamycin

哺乳动物雷帕霉素靶蛋白(mammalian target of rapamycin,mTOR)调节细胞存活、增殖和代谢。阿尔茨海默病(Alzheimer's disease,AD)是一种常见的神经系统退行性疾病,发病机理复杂,与衰老密切相关。研究发现,AD的病理发展过程中经常伴随着mTOR活性的变化,但尚不清楚mTOR在AD发病机制中的作用。本文首先介绍了mTOR的复合物及其信号通路,重点综述了mTOR信号通路对突触可塑性和记忆功能、自噬作用、β-淀粉样蛋白(amyloid-β,Aβ)、Tau蛋白和脑胰岛素抵抗等AD病理特征的影响,其次阐述了m TOR两种信号通路在抗衰老和延长寿命方面的调控作用,最后介绍了mTOR抑制剂在AD病理研究中的应用,为延缓和改善AD提供新的思路。

Mammalian target of rapamycin(mTOR)regulates cell survival,proliferation,and metabolism.Alzheimer's disease(AD)is a common neurodegenerative disease with a complex patho-genesis and is closely related to aging.Studies have found that the pathological development of AD is often accompanied by changes in mTOR activity,but the role of mTOR in the pathogenesis of AD is not clear.In this paper,the complex of mTOR and its signaling pathways are first introduced,focusing on the effects of mTOR signaling pathways on syn-aptic plasticity and memory function,autophagy,β-amyloid-β(Aβ),Tau protein and brain insulin resis-tance and other AD pathological features,secondly,the regulatory effects of mTOR signaling pathways in anti-aging and life prolongation are described,and finally the application of mTOR inhibitors in AD pathological research is introduced to provide new ideas for delaying and improving AD.