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小胶质细胞药理学的现状与未来。

Present and future of microglial pharmacology.

机构信息

Neuroscience Graduate Program, University of Victoria, Victoria, BC, Canada; Division of Medical Sciences, University of Victoria, Victoria, BC, Canada.

Division of Medical Sciences, University of Victoria, Victoria, BC, Canada.

出版信息

Trends Pharmacol Sci. 2022 Aug;43(8):669-685. doi: 10.1016/j.tips.2021.11.006. Epub 2022 Jan 11.

Abstract

Microglia, brain resident immune cells, modulate development, activity, and plasticity of the central nervous system. Mechanistically implicated in numerous neurological pathologies, microglia emerge as strong contenders for novel neurotherapies. Shifting away from merely an attenuation of excessive microglial inflammatory and phagocytic activities, current therapies aim toward targeting the complex context-dependent microglial heterogeneity, unveiled by large-scale genetic studies and emerging single-cell analyses. Although lacking the necessary selectivity, initial therapies attempting to target specific state-associated microglial properties and functions (e.g., inflammatory activity, phagocytosis, proliferation, metabolism, or surveillance) are currently under pre- or even clinical (Phase I-IV) investigation. Here, we provide an update on current microglial therapeutic research and discuss what the future in the field might look like.

摘要

小胶质细胞是大脑驻留的免疫细胞,可调节中枢神经系统的发育、活性和可塑性。小胶质细胞在许多神经病理学中具有重要作用,因此成为新型神经治疗的有力候选者。目前的治疗方法不再仅仅是减轻过度的小胶质细胞炎症和吞噬活性,而是针对大规模遗传研究和新兴单细胞分析揭示的复杂、依赖于背景的小胶质细胞异质性。尽管缺乏必要的选择性,但目前正在进行初始治疗,尝试针对特定状态相关的小胶质细胞特性和功能(例如炎症活性、吞噬作用、增殖、代谢或监视)进行治疗(例如,炎症活性、吞噬作用、增殖、代谢或监视)。目前正在进行初步或甚至临床(I-IV 期)研究。在这里,我们提供了对当前小胶质细胞治疗研究的最新更新,并讨论了该领域的未来前景。

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