Microglial Turnover in Ageing-Related Neurodegeneration: Therapeutic Avenue to Intervene in Disease Progression.
Microglial Turnover in Ageing-Related Neurodegeneration: Therapeutic Avenue to Intervene in Disease Progression.
复制标题
衰老相关神经退行性变中的小胶质细胞更新：干预疾病进展的治疗途径
DOI：
10.3390/cells10010150
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发表时间：
2021-01-14
期刊：
影响因子：
6
通讯作者：
Choi DK
中科院分区：
文献类型：
--
作者：
Azam S;Haque ME;Kim IS;Choi DK
小胶质细胞是驻留在大脑中的巨噬细胞，是神经免疫系统的主要组成部分，广泛参与中枢神经系统（CNS）的大脑发育、内稳态、衰老和损伤修复。与其他脑内巨噬细胞不同的是，它们能够持续感知大脑微环境的变化，充当神经元健康的守护者，并在正常生理状态下提供神经保护。小胶质细胞利用一组涉及促炎细胞因子的基因来实现这些功能。在受到特定刺激时，它们会释放这些促炎细胞因子，这些因子可通过神经炎症损伤和杀死神经元。然而，小胶质细胞功能的改变是与年龄相关的神经退行性疾病的常见病理生理学特征，例如阿尔茨海默病、帕金森病、亨廷顿病和朊病毒病，以及肌萎缩侧索硬化症、额颞叶痴呆和慢性创伤性脑病。当它们的监视或守护功能严重受损时，它们会通过过度刺激其防御功能以及神经炎症来加重神经病理状况。小胶质细胞的功能涉及多个通路，包括Trem2、Cx3cr1和颗粒蛋白前体通路，这些通路可控制小胶质细胞的炎症反应并促进有害刺激物的清除。随着时间的推移，该系统的失衡会导致具有保护作用的小胶质细胞变得有害，引发或加剧神经退行性变。纠正这种失衡可能是神经退行性疾病的一种潜在治疗干预方式。
Microglia are brain-dwelling macrophages and major parts of the neuroimmune system that broadly contribute to brain development, homeostasis, ageing and injury repair in the central nervous system (CNS). Apart from other brain macrophages, they have the ability to constantly sense changes in the brain’s microenvironment, functioning as housekeepers for neuronal well-being and providing neuroprotection in normal physiology. Microglia use a set of genes for these functions that involve proinflammatory cytokines. In response to specific stimuli, they release these proinflammatory cytokines, which can damage and kill neurons via neuroinflammation. However, alterations in microglial functioning are a common pathophysiology in age-related neurodegenerative diseases, such as Alzheimer’s, Parkinson’s, Huntington’s and prion diseases, as well as amyotrophic lateral sclerosis, frontotemporal dementia and chronic traumatic encephalopathy. When their sentinel or housekeeping functions are severely disrupted, they aggravate neuropathological conditions by overstimulating their defensive function and through neuroinflammation. Several pathways are involved in microglial functioning, including the Trem2, Cx3cr1 and progranulin pathways, which keep the microglial inflammatory response under control and promote clearance of injurious stimuli. Over time, an imbalance in this system leads to protective microglia becoming detrimental, initiating or exacerbating neurodegeneration. Correcting such imbalances might be a potential mode of therapeutic intervention in neurodegenerative diseases.
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影响因子：
4.1
作者：
Dickson DW
通讯作者：
Dickson DW
耦合的增殖和凋亡维持成人大脑中小胶质细胞的快速离职。
影响因子：
8.8
作者：
Askew K;Li K;Olmos-Alonso A;Garcia-Moreno F;Liang Y;Richardson P;Tipton T;Chapman MA;Riecken K;Beccari S;Sierra A;Molnár Z;Cragg MS;Garaschuk O;Perry VH;Gomez-Nicola D
通讯作者：
Gomez-Nicola D
CD36介导了对β-淀粉样蛋白的先天宿主反应。
影响因子：
15.3
作者：
El Khoury, JB;Moore, KJ;Means, TK;Leung, J;Terada, K;Toft, M;Freeman, MW;Luster, AD
通讯作者：
Luster, AD
影响因子：
16.6
作者：
Choi, Insup;Zhang, Yuanxi;Yue, Zhenyu
通讯作者：
Yue, Zhenyu
影响因子：
13.3
作者：
Cho, Mi-Hyang;Cho, Kwangmin;Yoon, Seung-Yong
通讯作者：
Yoon, Seung-Yong