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小胶质细胞与Wnt信号通路:阿尔茨海默病炎症反应的研究前景

Microglia and Wnt Pathways: Prospects for Inflammation in Alzheimer's Disease.

作者信息

Yang Yunying, Zhang Zhentao

机构信息

Department of Neurology, Renmin Hospital of Wuhan University, Wuhan, China.

出版信息

Front Aging Neurosci. 2020 May 14;12:110. doi: 10.3389/fnagi.2020.00110. eCollection 2020.

Abstract

Alzheimer's disease (AD) has been a major health issue for more than one century since it was first reported in 1906. As one of the most common neurodegenerative diseases, AD is characterized by the presence of senile plaques and neurofibrillary tangles (NFTs) in the affected brain area. Microglia are the major regulators of neuroinflammation in the brain, and neuroinflammation has become recognized as the core pathophysiological process of various neurodegenerative diseases. In the central nervous system (CNS), microglia play a dual role in AD development. For one thing, they degrade amyloid β (Aβ) to resist its deposition; for another, microglia release pro-inflammatory and inflammatory factors, contributing to neuroinflammation as well as the spreading of Aβ and tau pathology. Wnt pathways are important regulators of cell fate and cell activities. The dysregulation of Wnt pathways is responsible for both abnormal tau phosphorylation and synaptic loss in AD. Recent studies have also confirmed the regulatory effect of Wnt signaling on microglial inflammation. Thus, the study of microglia, Wnt pathways, and their possible interactions may open up a new direction for understanding the mechanisms of neuroinflammation in AD. In this review, we summarize the functions of microglia and Wnt pathways and their roles in AD in order to provide new ideas for understanding the pathogenesis of AD.

摘要

自1906年首次报道以来,阿尔茨海默病(AD)一直是一个重大的健康问题。作为最常见的神经退行性疾病之一,AD的特征是在受影响的脑区存在老年斑和神经原纤维缠结(NFTs)。小胶质细胞是大脑神经炎症的主要调节因子,神经炎症已被公认为各种神经退行性疾病的核心病理生理过程。在中枢神经系统(CNS)中,小胶质细胞在AD的发展中起双重作用。一方面,它们降解淀粉样β蛋白(Aβ)以抵抗其沉积;另一方面,小胶质细胞释放促炎和炎症因子,导致神经炎症以及Aβ和tau病理的传播。Wnt信号通路是细胞命运和细胞活动的重要调节因子。Wnt信号通路的失调是AD中tau异常磷酸化和突触丧失的原因。最近的研究也证实了Wnt信号对小胶质细胞炎症的调节作用。因此,对小胶质细胞、Wnt信号通路及其可能的相互作用的研究可能为理解AD中神经炎症的机制开辟一个新方向。在这篇综述中,我们总结了小胶质细胞和Wnt信号通路的功能及其在AD中的作用,以便为理解AD的发病机制提供新的思路。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/485a/7241259/4af0c63ba139/fnagi-12-00110-g001.jpg

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