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大麻素受体 2(CB2R)在神经保护对抗神经紊乱中的作用。

The impact of cannabinoid type 2 receptors (CB2Rs) in neuroprotection against neurological disorders.

机构信息

Institute of Brain Science and Diseases, and Department of Physiology, School of Basic Medicine, Qingdao University, Qingdao, 266071, China.

Institute of Neurobiology, Jining Medical University, Jining, 272000, China.

出版信息

Acta Pharmacol Sin. 2020 Dec;41(12):1507-1518. doi: 10.1038/s41401-020-00530-2. Epub 2020 Oct 6.

Abstract

Cannabinoids have long been used for their psychotropic and possible medical properties of symptom relief. In the past few years, a vast literature shows that cannabinoids are neuroprotective under different pathological situations. Most of the effects of cannabinoids are mediated by the well-characterized cannabinoid receptors, the cannabinoid type 1 receptor (CB1R) and cannabinoid type 2 receptor (CB2R). Even though CB1Rs are highly expressed in the central nervous system (CNS), the adverse central side effects and the development of tolerance resulting from CB1R activation may ultimately limit the clinical utility of CB1R agonists. In contrast to the ubiquitous presence of CB1Rs, CB2Rs are less commonly expressed in the healthy CNS but highly upregulated in glial cells under neuropathological conditions. Experimental studies have provided robust evidence that CB2Rs seem to be involved in the modulation of different neurological disorders. In this paper, we summarize the current knowledge regarding the protective effects of CB2R activation against the development of neurological diseases and provide a perspective on the future of this field. A better understanding of the fundamental pharmacology of CB2R activation is essential for the development of clinical applications and the design of novel therapeutic strategies.

摘要

大麻素因其致幻作用和可能具有缓解症状的医学特性而长期以来一直被使用。在过去的几年中,大量文献表明大麻素在不同的病理情况下具有神经保护作用。大麻素的大多数作用是通过特征明确的大麻素受体,即大麻素 1 型受体 (CB1R) 和大麻素 2 型受体 (CB2R) 介导的。尽管 CB1R 在中枢神经系统 (CNS) 中高度表达,但由于 CB1R 激活而导致的中枢副作用和耐受性的发展可能最终限制 CB1R 激动剂的临床应用。与 CB1R 普遍存在形成鲜明对比的是,CB2R 在健康的 CNS 中表达较少,但在神经病理学条件下在神经胶质细胞中高度上调。实验研究为 CB2R 似乎参与调节不同神经疾病提供了有力证据。在本文中,我们总结了 CB2R 激活对神经疾病发展的保护作用的最新知识,并对该领域的未来进行了展望。更好地了解 CB2R 激活的基础药理学对于临床应用的发展和新型治疗策略的设计至关重要。

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