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Toll样受体2信号传导与突触核蛋白病治疗调节的当前方法

Toll-Like Receptor 2 Signaling and Current Approaches for Therapeutic Modulation in Synucleinopathies.

作者信息

Caplan Ian F, Maguire-Zeiss Kathleen A

机构信息

Biology Department, Georgetown University, Washington, DC, United States.

Department of Neuroscience, Georgetown University Medical Center, Washington, DC, United States.

出版信息

Front Pharmacol. 2018 May 4;9:417. doi: 10.3389/fphar.2018.00417. eCollection 2018.

Abstract

The innate immune response in the central nervous system (CNS) is implicated as both beneficial and detrimental to health. Integral to this process are microglia, the resident immune cells of the CNS. Microglia express a wide variety of pattern-recognition receptors, such as Toll-like receptors, that detect changes in the neural environment. The activation of microglia and the subsequent proinflammatory response has become increasingly relevant to synucleinopathies, including Parkinson's disease the second most prevalent neurodegenerative disease. Within these diseases there is evidence of the accumulation of endogenous α-synuclein that stimulates an inflammatory response from microglia via the Toll-like receptors. There have been recent developments in both new and old pharmacological agents designed to target microglia and curtail the inflammatory environment. This review will aim to delineate the process of microglia-mediated inflammation and new therapeutic avenues to manage the response.

摘要

中枢神经系统(CNS)中的先天免疫反应对健康既有益处也有损害。在此过程中起重要作用的是小胶质细胞,即中枢神经系统中的常驻免疫细胞。小胶质细胞表达多种模式识别受体,如Toll样受体,可检测神经环境的变化。小胶质细胞的激活及随后的促炎反应与包括帕金森病(第二常见的神经退行性疾病)在内的突触核蛋白病的相关性日益增加。在这些疾病中,有证据表明内源性α-突触核蛋白积累,通过Toll样受体刺激小胶质细胞产生炎症反应。最近,在旨在靶向小胶质细胞并减少炎症环境的新旧药物方面都有进展。本综述旨在描述小胶质细胞介导的炎症过程以及控制该反应的新治疗途径。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/11de/5945810/0c4031d40254/fphar-09-00417-g0001.jpg

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