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小胶质细胞自噬和线粒体自噬在年龄相关性神经退行性疾病中的作用。

Role of microglia autophagy and mitophagy in age-related neurodegenerative diseases.

作者信息

Lin Mingkai, Yu Hongwen, Xie Qiuyan, Xu Zhiyun, Shang Pei

机构信息

Department of Stomatology, Nanfang Hospital, Southern Medical University, Guangzhou, China.

Nanfang Hospital, Southern Medical University, Guangzhou, China.

出版信息

Front Aging Neurosci. 2023 Apr 26;14:1100133. doi: 10.3389/fnagi.2022.1100133. eCollection 2022.

Abstract

Microglia, characterized by responding to damage, regulating the secretion of soluble inflammatory mediators, and engulfing specific segments in the central nervous system (CNS), function as key immune cells in the CNS. Emerging evidence suggests that microglia coordinate the inflammatory responses in CNS system and play a pivotal role in the pathogenesis of age-related neurodegenerative diseases (NDDs). Remarkably, microglia autophagy participates in the regulation of subcellular substances, which includes the degradation of misfolded proteins and other harmful constituents produced by neurons. Therefore, microglia autophagy regulates neuronal homeostasis maintenance and process of neuroinflammation. In this review, we aimed at highlighting the pivotal role of microglia autophagy in the pathogenesis of age-related NDDs. Besides the mechanistic process and the co-interaction between microglia autophagy and different kinds of NDDs, we also emphasized potential therapeutic agents and approaches that could be utilized at the onset and progression of these diseases through modulating microglia autophagy, including promising nanomedicines. Our review provides a valuable reference for subsequent studies focusing on treatments of neurodegenerative disorders. The exploration of microglia autophagy and the development of nanomedicines greatly enhances current understanding of NDDs.

摘要

小胶质细胞的特征是对损伤做出反应、调节可溶性炎症介质的分泌以及吞噬中枢神经系统(CNS)中的特定片段,在中枢神经系统中发挥关键免疫细胞的作用。新出现的证据表明,小胶质细胞协调中枢神经系统中的炎症反应,并在年龄相关性神经退行性疾病(NDDs)的发病机制中起关键作用。值得注意的是,小胶质细胞自噬参与亚细胞物质的调节,包括错误折叠蛋白和神经元产生的其他有害成分的降解。因此,小胶质细胞自噬调节神经元内环境稳态的维持和神经炎症过程。在本综述中,我们旨在强调小胶质细胞自噬在年龄相关性神经退行性疾病发病机制中的关键作用。除了小胶质细胞自噬的机制过程以及与不同类型神经退行性疾病之间的共同相互作用外,我们还强调了在这些疾病的发病和进展过程中可通过调节小胶质细胞自噬来利用的潜在治疗药物和方法,包括有前景的纳米药物。我们的综述为后续关注神经退行性疾病治疗的研究提供了有价值的参考。对小胶质细胞自噬的探索和纳米药物的开发极大地增进了当前对神经退行性疾病的理解。

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