Preprint Review Version 1 Preserved in Portico This version is not peer-reviewed

Novel Mechanistic Insights and Potential Therapeutic Impact of TRPC6 in Neurovascular Coupling and Ischemic Stroke

Shashank Shekhar
* ORCID logo ,
Yedan Liu
,
Shaoxun Wang
,
Huawei Zhang
,
Xing Fang
,
Jin Zhang
,
Letao Fan
ORCID logo ,
Baoying Zheng
,
Richard Roman
ORCID logo ,
Zhen Wang
,
Fan Fan
ORCID logo ,
George Booz
Version 1 : Received: 22 January 2021 / Approved: 25 January 2021 / Online: 25 January 2021 (09:20:51 CET)

A peer-reviewed article of this Preprint also exists.

Shekhar, S.; Liu, Y.; Wang, S.; Zhang, H.; Fang, X.; Zhang, J.; Fan, L.; Zheng, B.; Roman, R.J.; Wang, Z.; Fan, F.; Booz, G.W. Novel Mechanistic Insights and Potential Therapeutic Impact of TRPC6 in Neurovascular Coupling and Ischemic Stroke. Int. J. Mol. Sci. 2021, 22, 2074. Shekhar, S.; Liu, Y.; Wang, S.; Zhang, H.; Fang, X.; Zhang, J.; Fan, L.; Zheng, B.; Roman, R.J.; Wang, Z.; Fan, F.; Booz, G.W. Novel Mechanistic Insights and Potential Therapeutic Impact of TRPC6 in Neurovascular Coupling and Ischemic Stroke. Int. J. Mol. Sci. 2021, 22, 2074.

Abstract

Ischemic stroke is one of the most disabling diseases and a leading cause of death globally. Despite advances in medical care, the global burden of stroke continues to grow, as no effective treatments to limit or reverse ischemic injury to the brain are available. However, recent preclinical findings have revealed the potential role of transient receptor potential cation 6 (TRPC6) channels as endogenous protectors of neuronal tissue. Activating TRPC6 in various cerebral ischemia models has been found to prevent neuronal death, whereas blocking TRPC6 enhances sensitivity to ischemia. Evidence has shown that Ca2+ influx through TRPC6 activates cAMP response element-binding protein (CREB), an important transcription factor linked to neuronal survival. Additionally, TRPC6 activation may counter excitotoxic damage resulting from glutamate release by attenuating the activity of NMDA receptors of neurons by posttranslational means. Unresolved though, are the roles of TRPC6 channels in non-neuronal cells such as astrocytes and endothelial cells. Moreover, TRPC6 channels may have detrimental effects on the blood-brain barrier, although their exact role in neurovascular coupling requires further investigation. This review discusses evidence-based cell-specific aspects of TRPC6 in the brain to assess the potential targets for ischemic stroke management.

Keywords

blood-brain barrier; transient receptor potential cation channels; ischemic stroke; neuroprotection; calcium signaling; cAMP response element-binding protein

Subject

Medicine and Pharmacology, Immunology and Allergy

Copyright: This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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