Novel Targets for Stroke Therapy: Special Focus on TRPC Channels and TRPC6 - PubMed (original) (raw)

Review

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

Lu Liu et al. Front Aging Neurosci. 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 Ca2+ 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.

Keywords: TRP ion channels; TRPC6 channel; TRPCs; ischemic stroke; neuronal survival.

Copyright © 2020 Liu, Gu, Chen, Zheng, Xiong and Zhu.

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Figures

FIGURE 1

FIGURE 1

Structural features of TRPC6 channel. (A) Transmembrane protein TRPC6 contains six TDs, four NH2-terminal ARDs, and a COOH-terminal TRP domain. (B) S1–S6 are TDs. The pore region of TRPC6, situated between the S5 and S6, allows the passage of cations. TRP: transient receptor potential; TRPC6: transient receptor potential canonical channel 6; TD: transmembrane domain; ARD: ankyrin repeat domain; S1–S6: S1–S6 are the abbreviations of the first to sixth transmembrane domains.

FIGURE 2

FIGURE 2

Underlying signaling cascade of TRPC6 in ischemic stroke. TRPC6/Ca2+/CAMKIV/CREB pathway is closely involved in the pathophysiological mechanism of cerebral IR injury. TRPC6: transient receptor potential canonical channel 6; Ca2+: calcium; CAMKIV: Ca2+/calmodulin-dependent kinase IV; CREB: cAMP-response element binding protein; NF-κB: nuclear factor (NF)-κB.

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