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中风治疗的新靶点:特别关注瞬时受体电位通道蛋白(TRPC)通道和TRPC6

Novel Targets for Stroke Therapy: Special Focus on TRPC Channels and TRPC6.

作者信息

Liu Lu, Gu Lijuan, Chen Manli, Zheng Yueying, Xiong Xiaoxing, Zhu Shengmei

机构信息

Department of Anesthesiology, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, China.

Central Laboratory, Renmin Hospital of Wuhan University, Wuhan, China.

出版信息

Front Aging Neurosci. 2020 Mar 18;12:70. doi: 10.3389/fnagi.2020.00070. eCollection 2020.

Abstract

Stroke remains a leading cause of death, disability, and medical care burden worldwide. However, transformation from laboratory findings toward effective pharmacological interventions for clinical stroke has been unsatisfactory. Novel evidence has been gained on the underlying mechanisms and therapeutic potential related to the transient receptor potential (TRP) channels in several disorders. The TRP superfamily consists of a diverse group of Ca permeable non-selective cation channels. In particular, the members of TRP subfamilies, TRP canonical (TRPC) channels and TRPC6, have been found in different cell types in the whole body and have high levels of expression in the central nervous system (CNS). Notably, the TRPCs and TRPC6 channel have been implicated in neurite outgrowth and neuronal survival during normal development and in a range of CNS pathological conditions. Recent studies have shown that suppression of TRPC6 channel degradation prevents ischemic neuronal cell death in experimental stroke. Accumulating evidence supports the important functions of TRPC6 in brain ischemia. We have highlighted some crucial advancement that points toward an important involvement of TRPCs and TRPC6 in ischemic stroke. This review will make an overview of the TRP and TRPC channels due to their roles as targets for clinical trials and CNS disorders. Besides, the primary goal is to discuss and update the critical role of TRPC6 channels in stroke and provide a promising target for stroke prevention and therapy.

摘要

中风仍然是全球范围内导致死亡、残疾和医疗负担的主要原因。然而,从实验室研究结果转化为针对临床中风的有效药物干预一直不尽人意。在几种疾病中,关于瞬时受体电位(TRP)通道的潜在机制和治疗潜力已经获得了新的证据。TRP超家族由一组多样的钙通透性非选择性阳离子通道组成。特别是,TRP亚家族的成员,即TRP经典(TRPC)通道和TRPC6,已在全身不同细胞类型中发现,并在中枢神经系统(CNS)中具有高水平的表达。值得注意的是,TRPCs和TRPC6通道在正常发育过程以及一系列CNS病理状况下的神经突生长和神经元存活中发挥作用。最近的研究表明,抑制TRPC6通道降解可防止实验性中风中缺血性神经元细胞死亡。越来越多的证据支持TRPC6在脑缺血中的重要功能。我们强调了一些关键进展,这些进展表明TRPCs和TRPC6在缺血性中风中具有重要作用。由于TRP和TRPC通道作为临床试验和CNS疾病的靶点所起的作用,本综述将对其进行概述。此外,主要目标是讨论并更新TRPC6通道在中风中的关键作用,并为中风预防和治疗提供一个有前景的靶点。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/250a/7093711/63828da6090f/fnagi-12-00070-g001.jpg

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