Wnt/β-catenin信号通路在阿尔茨海默病神经元变性中的研究进展

Research advances in the Wnt/β-catenin signaling pathway in neuronal degeneration in Alzheimer's Disease

目的:阿尔茨海默病(Alzheimer’s disease,AD)是目前老年人最常见的痴呆类型,由于AD发病机制复杂,迄今尚未完全阐明。AD最重要的神经病理学特征是β淀粉样蛋白(amyloid-βprotein,Aβ)沉积、Tau蛋白过度磷酸化形成神经纤维缠结以及脑内神经炎症反应的激活,并伴随着神经元的损伤及学习记忆功能受损。越来越多的研究指出Wnt/β-连环蛋白(Wnt/β-catenin)信号通路在神经退行性疾病中,尤其是AD中发挥了重要作用。为明确Wnt/β-catenin信号通路与AD发病、Aβ沉积、Tau蛋白和神经炎症的相关性及其机制,对相关文献进行综述。方法:选择Wnt/β-catenin信号通路与AD、Aβ神经毒性、Tau蛋白磷酸化及神经炎症相关的国内外相关文献进行综述。结果:研究表明Wnt/β-catenin信号通路参与AD的发生和发展,当该通路激活时可以抑制Aβ的沉积、Tau的过度磷酸化及神经炎症,反之则促进Aβ的产生、聚集以及Tau蛋白的磷酸化,神经炎症的发生。结论:本文就Wnt/β-catenin信号途径在AD发病中的重要性加以概述,为AD机制的研究提供了理论基础,也提示激活Wnt信号传导途径可以作为治疗AD的潜在治疗靶点。

Objective:Alzheimer’s disease(AD)is the most common type of dementia in the elderly,but its pathogenesis is complex and remains unclear.The most common neuropathological features of AD include amyloidβ-protein(Aβ)deposition,neurofibrillary tangles due to hyperphosphorylation of Tau protein,and the activation of brain neuroinflammation,with neuronal injury and impaired learning and memory abilities.A growing number of studies have shown that the Wnt/β-catenin signaling pathway plays an important role in neurodegenerative disorders,especially in AD.This article reviews the related literature to clarify the association of the Wnt/β-catenin signaling pathway with the pathogenesis of AD,Aβdeposition,Tau protein,and neuroinflammation and related mechanism.Methods:The articles on the association of the Wnt/β-catenin signaling pathway with AD,Aβneurotoxicity,Tau protein phosphorylation,and neuroinflammation,published in China and foreign countries,were reviewed.Results:Studies showed that the Wnt/β-catenin signaling pathway was involved in the development and progression of AD.The activation of this pathway inhibited Aβdeposition,hyperphosphorylation of Tau protein,and neuroinflammation,and on the contrary,it promoted the formation and aggregation of Aβ,the phosphorylation of Tau protein,and the development of neuroinflammation.Conclusion:This article reviews the importance of the Wnt/β-catenin signaling pathway in the pathogenesis of AD and provides a theoretical basis for the research on the pathogenesis of AD.It is pointed out that activation of the Wnt/β-catenin signaling pathway may be used as a potential target for the treatment of AD.