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Sigma-1 Receptor: A Potential Therapeutic Target for Traumatic Brain Injury

The sigma-1 receptor (Sig-1R) is a chaperone receptor that primarily resides at the mitochondria-associated endoplasmic reticulum (ER) membrane (MAM) and acts as a dynamic pluripotent modulator regulating cellular pathophysiological processes. Multiple pharmacological studies have confirmed the bene...

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Autores principales: Shi, Mingming, Chen, Fanglian, Chen, Zhijuan, Yang, Weidong, Yue, Shuyuan, Zhang, Jianning, Chen, Xin
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8515188/
https://www.ncbi.nlm.nih.gov/pubmed/34658788
http://dx.doi.org/10.3389/fncel.2021.685201
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author Shi, Mingming
Chen, Fanglian
Chen, Zhijuan
Yang, Weidong
Yue, Shuyuan
Zhang, Jianning
Chen, Xin
author_facet Shi, Mingming
Chen, Fanglian
Chen, Zhijuan
Yang, Weidong
Yue, Shuyuan
Zhang, Jianning
Chen, Xin
author_sort Shi, Mingming
collection PubMed
description The sigma-1 receptor (Sig-1R) is a chaperone receptor that primarily resides at the mitochondria-associated endoplasmic reticulum (ER) membrane (MAM) and acts as a dynamic pluripotent modulator regulating cellular pathophysiological processes. Multiple pharmacological studies have confirmed the beneficial effects of Sig-1R activation on cellular calcium homeostasis, excitotoxicity modulation, reactive oxygen species (ROS) clearance, and the structural and functional stability of the ER, mitochondria, and MAM. The Sig-1R is expressed broadly in cells of the central nervous system (CNS) and has been reported to be involved in various neurological disorders. Traumatic brain injury (TBI)-induced secondary injury involves complex and interrelated pathophysiological processes such as cellular apoptosis, glutamate excitotoxicity, inflammatory responses, endoplasmic reticulum stress, oxidative stress, and mitochondrial dysfunction. Thus, given the pluripotent modulation of the Sig-1R in diverse neurological disorders, we hypothesized that the Sig-1R may affect a series of pathophysiology after TBI. This review summarizes the current knowledge of the Sig-1R, its mechanistic role in various pathophysiological processes of multiple CNS diseases, and its potential therapeutic role in TBI.
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spelling pubmed-85151882021-10-15 Sigma-1 Receptor: A Potential Therapeutic Target for Traumatic Brain Injury Shi, Mingming Chen, Fanglian Chen, Zhijuan Yang, Weidong Yue, Shuyuan Zhang, Jianning Chen, Xin Front Cell Neurosci Neuroscience The sigma-1 receptor (Sig-1R) is a chaperone receptor that primarily resides at the mitochondria-associated endoplasmic reticulum (ER) membrane (MAM) and acts as a dynamic pluripotent modulator regulating cellular pathophysiological processes. Multiple pharmacological studies have confirmed the beneficial effects of Sig-1R activation on cellular calcium homeostasis, excitotoxicity modulation, reactive oxygen species (ROS) clearance, and the structural and functional stability of the ER, mitochondria, and MAM. The Sig-1R is expressed broadly in cells of the central nervous system (CNS) and has been reported to be involved in various neurological disorders. Traumatic brain injury (TBI)-induced secondary injury involves complex and interrelated pathophysiological processes such as cellular apoptosis, glutamate excitotoxicity, inflammatory responses, endoplasmic reticulum stress, oxidative stress, and mitochondrial dysfunction. Thus, given the pluripotent modulation of the Sig-1R in diverse neurological disorders, we hypothesized that the Sig-1R may affect a series of pathophysiology after TBI. This review summarizes the current knowledge of the Sig-1R, its mechanistic role in various pathophysiological processes of multiple CNS diseases, and its potential therapeutic role in TBI. Frontiers Media S.A. 2021-09-30 /pmc/articles/PMC8515188/ /pubmed/34658788 http://dx.doi.org/10.3389/fncel.2021.685201 Text en Copyright © 2021 Shi, Chen, Chen, Yang, Yue, Zhang and Chen. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Neuroscience
Shi, Mingming
Chen, Fanglian
Chen, Zhijuan
Yang, Weidong
Yue, Shuyuan
Zhang, Jianning
Chen, Xin
Sigma-1 Receptor: A Potential Therapeutic Target for Traumatic Brain Injury
title Sigma-1 Receptor: A Potential Therapeutic Target for Traumatic Brain Injury
title_full Sigma-1 Receptor: A Potential Therapeutic Target for Traumatic Brain Injury
title_fullStr Sigma-1 Receptor: A Potential Therapeutic Target for Traumatic Brain Injury
title_full_unstemmed Sigma-1 Receptor: A Potential Therapeutic Target for Traumatic Brain Injury
title_short Sigma-1 Receptor: A Potential Therapeutic Target for Traumatic Brain Injury
title_sort sigma-1 receptor: a potential therapeutic target for traumatic brain injury
topic Neuroscience
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8515188/
https://www.ncbi.nlm.nih.gov/pubmed/34658788
http://dx.doi.org/10.3389/fncel.2021.685201
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