药学学报, 2021, 56(2): 383-390
李凌杰, 于晓琳, 刘瑞田. 胶质细胞介导的神经突触修剪在阿尔茨海默病中的作用[J]. 药学学报, 2021, 56(2): 383-390.
LI Ling-jie, YU Xiao-lin, LIU Rui-tian. Synaptic pruning mediated by glia in Alzheimer's disease[J]. Acta Pharmaceutica Sinica, 2021, 56(2): 383-390.

李凌杰1,2, 于晓琳1, 刘瑞田1
1. 中国科学院过程工程研究所, 生化工程国家重点实验室, 北京 100190;
2. 中国科学院大学, 化学与化工学院, 北京 100049
阿尔茨海默病(Alzheimer's disease,AD)是一种以记忆丧失、认知障碍为主要特征的神经退行性疾病,迄今尚无有效的治疗策略。神经突触是大脑神经元之间联系的部位,是产生记忆及其他神经活动的关键组成部分,神经突触的丢失是AD的重要病理特征。胶质细胞是大脑中除神经元以外的一类至关重要的细胞,其中最主要的两类胶质细胞为小胶质细胞和星形胶质细胞。胶质细胞在维持大脑健康神经环路和调节神经突触可塑性方面扮演着重要角色。在正常生理状态下,胶质细胞通过修剪多余的神经突触构建和维持成熟的中枢神经网络。然而,在AD的发生和发展过程中,胶质细胞对神经突触过度地修剪和清除,导致突触大量丢失,引发神经元功能紊乱或死亡,从而造成认知能力损伤。基于此,本文拟对目前AD中小胶质细胞和星形胶质细胞参与突触修剪的可能机制进行综述,以期为AD治疗药物的研发提供崭新的思路。
关键词:    阿尔茨海默病      认知障碍      小胶质细胞      星形胶质细胞      突触修剪     
Synaptic pruning mediated by glia in Alzheimer's disease
LI Ling-jie1,2, YU Xiao-lin1, LIU Rui-tian1
1. State Key Laboratory of Biochemical Engineering, Institute of Process Engineering, Chinese Academy of Sciences, Beijing 100190, China;
2. School of Chemistry and Chemical Engineering, University of Chinese Academy of Sciences, Beijing 100049, China
Alzheimer's disease (AD) is a neurodegenerative disease characterized by memory loss and cognitive impairment. To date, however, no disease-modifying strategies to prevent or cure AD exist. Synapses are involved in the connection of neurons and present as the key component for the memory and other neural activities. Synapse loss is a critical hallmark of AD pathology. In brain, glia cells, including microglia and astrocytes, are a group of highly specific cell types other than neurons. Microglia and astrocytes play a key role in maintaining the healthy neural circuit and regulating synaptic plasticity. Under development and physiological conditions, glial cells contribute to construct and maintain mature central neural networks via synaptic pruning. However, during AD pathogenesis, glial cells engulf synapses excessively, which leads to synapse loss, neuronal dysfunction, and cognitive impairment. Here, we review recent advances in our understanding of the underlying mechanisms for glia-mediated synaptic pruning in AD, and provide a novel strategy for the development of AD drugs.
Key words:    Alzheimer's disease    cognitive deficit    microglia    astrocyte    synaptic pruning   
收稿日期: 2020-10-21
DOI: 10.16438/j.0513-4870.2020-1640
基金项目: 国家自然科学基金资助项目(81971610).
通讯作者: 于晓琳,Tel:86-10-82545075,E-mail:yuxiaolin@ipe.ac.cn;刘瑞田,Tel:86-10-82545017,E-mail:rtliu@ipe.ac.cn
Email: yuxiaolin@ipe.ac.cn;rtliu@ipe.ac.cn
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