《生命科学》 2021, 33(8): 946-954

星形胶质细胞参与阿尔茨海默病早期突触功能损伤的研究进展

刘　聪 , 沈　逸^*

浙江大学脑科学与脑医学学院，卫生部医学神经生物学重点实验室，杭州 310058

摘　要：

阿尔茨海默病(Alzheimer’s disease, AD) 是以β 淀粉样蛋白(amyloid β, Aβ) 沉积和神经纤维缠结(neurofibrillary tangles, NFTs) 等病理特征及记忆衰退等临床特征为标志的一种神经退行性疾病。AD 的主要症状认知障碍与突触减少密切相关。可溶性寡聚Aβ 引起的突触功能损伤是AD 早期病理机制研究的热点。星形胶质细胞对突触功能调控起重要作用，其功能改变与AD 病理表现密切相关。星形胶质细胞可以通过参与Aβ 代谢、中枢炎性反应、突触调控和胞内钙信号传递等途径参与AD 早期的突触功能损伤。该文对近年来星形胶质细胞在AD 早期突触功能损伤中的主要作用及机制进行综述，同时对这一领域的开放问题进行了归纳。

通讯作者：沈　逸 , Email:yshen2@zju.edu.cn

The role of astrocyte regulating synapse dysfunction in early Alzheimer’s disease

LIU Cong , SHEN Yi^*

Department of Neurobiology, Zhejiang University School of Medicine, Hangzhou 310058, Chin

Abstract:

Alzheimer’s disease (AD), a neurodegenerative disease, is characterized by the presence of extracellular amyloid-β (Aβ) aggregates and intracellular neurofibrillary tangles formed by hyperphosphorylated tau as pathological features and the cognitive decline as main clinical feature. An important cellular correlation of cognitive decline in AD is synapse loss. Soluble Aβ oligomer has been proposed to be a crucial early event leading to synapse dysfunction in AD. Astrocytes are crucial for synaptic formation and function, and defects in astrocytic activation and function have been suggested in the pathogenesis of AD. Astrocytes may contribute to synapse dysfunction at an early stage of AD by participating in Aβ metabolism, brain inflammatory response, synaptic regulation, and intracellular calcium signaling. In this review, we describe the role of astrocytes and underlying mechanisms in regulating synapse dysfunction in early AD, and discuss the open questions in this field.

Communication Author：SHEN Yi , Email:yshen2@zju.edu.cn