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黑色素瘤 2 缺失(AIM2)炎症小体在中枢神经系统疾病中的新兴作用。

The emerging roles of absent in melanoma 2 (AIM2) inflammasome in central nervous system disorders.

机构信息

Department of Pharmacology, School of Basic Medicine, Tongji Medical College, Huazhong University of Science and Technology, 430030, Wuhan, China.

Department of Pharmacology, School of Basic Medicine, Tongji Medical College, Huazhong University of Science and Technology, 430030, Wuhan, China; The Research Center for Depression, Tongji Medical College, Huazhong University of Science, 430030, Wuhan, China; The Key Laboratory for Drug Target Researches and Pharmacodynamic Evaluation of Hubei Province, 430030, Wuhan, China.

出版信息

Neurochem Int. 2021 Oct;149:105122. doi: 10.1016/j.neuint.2021.105122. Epub 2021 Jul 17.

Abstract

As a double-stranded DNA (dsDNA) sensor, the PYHIN family member absent in melanoma 2 (AIM2) is an essential component of the inflammasome families. Activation of AIM2 by dsDNA leads to the assembly of cytosolic multimolecular complexes termed the AIM2 inflammasome, resulting in activation of caspase-1, the maturation and secretion of pro-inflammatory cytokines interleukin (IL)-1β and IL-18, and pyroptosis. Multiple central nervous system (CNS) diseases are accompanied by immune responses and inflammatory cascade. As the resident macrophage cells, microglia cells act as the first and main form of active immune defense in the CNS. AIM2 is highly expressed in microglia as well as astrocytes and neurons and is essential in neurodevelopment. In this review, we highlight the recent progress on the role of AIM2 inflammasome in CNS disorders, including cerebral stroke, brain injury, neuropsychiatric disease, neurodegenerative diseases, and glioblastoma.

摘要

作为双链 DNA (dsDNA) 传感器,黑色素瘤缺失 2 型 (AIM2) 家族成员 PYHIN 是炎症小体家族的重要组成部分。dsDNA 激活 AIM2 导致细胞溶质多分子复合物的组装,称为 AIM2 炎症小体,导致半胱天冬酶-1 的激活、促炎细胞因子白细胞介素 (IL)-1β 和 IL-18 的成熟和分泌以及细胞焦亡。多种中枢神经系统 (CNS) 疾病伴有免疫反应和炎症级联。作为驻留巨噬细胞,小胶质细胞在 CNS 中充当主动免疫防御的第一和主要形式。AIM2 在小胶质细胞以及星形胶质细胞和神经元中高度表达,在神经发育中至关重要。在这篇综述中,我们强调了 AIM2 炎症小体在包括脑卒中和脑损伤在内的 CNS 疾病、神经精神疾病、神经退行性疾病和神经胶质瘤中的作用的最新进展。

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