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反应性星形胶质细胞作为脑退行性疾病的治疗靶点:代谢型谷氨酸受体的作用。

Reactive Astrocytes as Therapeutic Targets for Brain Degenerative Diseases: Roles Played by Metabotropic Glutamate Receptors.

机构信息

Joint Graduate Program in Toxicology, Rutgers, The State University of New Jersey, Piscataway, NJ, USA.

Department of Neuroscience and Cell Biology, Rutgers Robert Wood Johnson Medical School, Piscataway, NJ, USA.

出版信息

Neurochem Res. 2020 Mar;45(3):541-550. doi: 10.1007/s11064-020-02968-6. Epub 2020 Jan 25.

Abstract

Astrocytes are well known to play critical roles in the development and maintenance of the central nervous system (CNS). Moreover, recent reports indicate that these cells are heterogeneous with respect to the molecules they express and the functions they exhibit in the quiescent or activated state. Because astrocytes also contribute to pathology, promising new results raise the possibility of manipulating specific astroglial populations for therapeutic roles. In this mini-review, we highlight the function of metabotropic glutamate receptors (mGluRs), in particular mGluR3 and mGluR5, in reactive astrocytes and relate these to three degenerative CNS diseases: multiple sclerosis, Alzheimer's disease and Amyotrophic Lateral Sclerosis. Previous studies demonstrate that effects of these receptors may be beneficial, but this varies depending on the subtype of receptor, the state of the astrocytes, and the specific disease to which they are exposed. Elucidating the role of mGluRs on astrocytes at specific times during development and disease will provide novel insights in understanding how to best use these to serve as therapeutic targets.

摘要

星形胶质细胞在中枢神经系统 (CNS) 的发育和维持中起着至关重要的作用,这是众所周知的。此外,最近的报告表明,这些细胞在表达的分子和在静息或激活状态下表现出的功能方面具有异质性。由于星形胶质细胞也与病理学有关,有希望的新结果提出了操纵特定星形胶质细胞群体以发挥治疗作用的可能性。在这篇迷你综述中,我们强调代谢型谷氨酸受体 (mGluRs),特别是 mGluR3 和 mGluR5,在反应性星形胶质细胞中的作用,并将这些与三种退行性中枢神经系统疾病联系起来:多发性硬化症、阿尔茨海默病和肌萎缩侧索硬化症。先前的研究表明,这些受体的作用可能是有益的,但这取决于受体的亚型、星形胶质细胞的状态以及它们所暴露的特定疾病。阐明 mGluRs 在发育和疾病特定时期对星形胶质细胞的作用将为理解如何最好地利用它们作为治疗靶点提供新的见解。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a13d/7058558/9303884dabe2/11064_2020_2968_Fig1_HTML.jpg

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