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星形胶质细胞衰老与阿尔茨海默病:综述

Astrocyte Senescence and Alzheimer's Disease: A Review.

作者信息

Han Xiaojuan, Zhang Tianying, Liu Huanhuan, Mi Yajing, Gou Xingchun

机构信息

Shaanxi Key Laboratory of Brain Disorders & Institute of Basic and Translational Medicine, Xi'an Medical University, Xi'an, China.

出版信息

Front Aging Neurosci. 2020 Jun 9;12:148. doi: 10.3389/fnagi.2020.00148. eCollection 2020.

Abstract

Astrocytes are the largest group of glial cells in the brain and participate in several essential functions of the central nervous system (CNS). Disruption of their normal physiological function can lead to metabolism disequilibrium and the pathology of CNS. As an important mechanism of aging, cellular senescence has been considered as a primary inducing factor of age-associated neurodegenerative disorders. Senescent astrocytes showed decreased normal physiological function and increased secretion of senescence-associated secretory phenotype (SASP) factors, which contribute to Aβ accumulation, tau hyperphosphorylation, and the deposition of neurofibrillary tangles (NFTs) in Alzheimer's disease (AD). Astrocyte senescence also leads to a number of detrimental effects, including induced glutamate excitotoxicity, impaired synaptic plasticity, neural stem cell loss, and blood-brain barrier (BBB) dysfunction. In this review article, we have summarized the growing findings regarding astrocyte senescence and its putative role in the pathologic progress of AD. Additionally, we also focus on the significance of targeting astrocyte senescence as a novel and feasible therapeutic approach for AD.

摘要

星形胶质细胞是大脑中最大的神经胶质细胞群,参与中枢神经系统(CNS)的多种重要功能。其正常生理功能的破坏会导致代谢失衡和中枢神经系统病变。作为衰老的一种重要机制,细胞衰老被认为是与年龄相关的神经退行性疾病的主要诱导因素。衰老的星形胶质细胞正常生理功能下降,衰老相关分泌表型(SASP)因子分泌增加,这在阿尔茨海默病(AD)中促成了β淀粉样蛋白(Aβ)积累、tau蛋白过度磷酸化以及神经原纤维缠结(NFTs)的沉积。星形胶质细胞衰老还会导致许多有害影响,包括诱导谷氨酸兴奋性毒性、损害突触可塑性、神经干细胞丢失和血脑屏障(BBB)功能障碍。在这篇综述文章中,我们总结了关于星形胶质细胞衰老及其在AD病理进程中假定作用的越来越多的研究发现。此外,我们还关注将靶向星形胶质细胞衰老作为一种针对AD的新颖且可行的治疗方法的意义。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fb6c/7297132/58b6fcab58f9/fnagi-12-00148-g001.jpg

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