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Sigma-1 Receptor Agonist TS-157 Improves Motor Functional Recovery by Promoting Neurite Outgrowth and pERK in Rats with Focal Cerebral Ischemia

Sigma-1 (σ-1) receptor agonists are considered as potential treatment for stroke. TS-157 is an alkoxyisoxazole-based σ-1 receptor agonist previously discovered in our group. The present study describes TS-157 profile in a battery of tests for cerebral ischemia. Initial evaluation demonstrated the co...

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Autores principales: Shi, Jun-Jie, Jiang, Qi-Hui, Zhang, Tian-Ning, Sun, Hao, Shi, Wen-Wen, Gunosewoyo, Hendra, Yang, Fan, Tang, Jie, Pang, Tao, Yu, Li-Fang
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7956808/
https://www.ncbi.nlm.nih.gov/pubmed/33668340
http://dx.doi.org/10.3390/molecules26051212
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author Shi, Jun-Jie
Jiang, Qi-Hui
Zhang, Tian-Ning
Sun, Hao
Shi, Wen-Wen
Gunosewoyo, Hendra
Yang, Fan
Tang, Jie
Pang, Tao
Yu, Li-Fang
author_facet Shi, Jun-Jie
Jiang, Qi-Hui
Zhang, Tian-Ning
Sun, Hao
Shi, Wen-Wen
Gunosewoyo, Hendra
Yang, Fan
Tang, Jie
Pang, Tao
Yu, Li-Fang
author_sort Shi, Jun-Jie
collection PubMed
description Sigma-1 (σ-1) receptor agonists are considered as potential treatment for stroke. TS-157 is an alkoxyisoxazole-based σ-1 receptor agonist previously discovered in our group. The present study describes TS-157 profile in a battery of tests for cerebral ischemia. Initial evaluation demonstrated the compound’s safety profile and blood–brain barrier permeability, as well as its ability to induce neurite outgrowth in vitro. The neurite outgrowth was shown to be mediated via σ-1 receptor agonism and involves upregulation of ERK phosphorylation (pERK). In particular, TS-157 also significantly accelerated the recovery of motor function in rats with transient middle cerebral artery occlusion (tMCAO). Overall, the results herein support the notion that σ-1 receptor agonists are potential therapeutics for stroke and further animal efficacy studies are warranted.
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spelling pubmed-79568082021-03-16 Sigma-1 Receptor Agonist TS-157 Improves Motor Functional Recovery by Promoting Neurite Outgrowth and pERK in Rats with Focal Cerebral Ischemia Shi, Jun-Jie Jiang, Qi-Hui Zhang, Tian-Ning Sun, Hao Shi, Wen-Wen Gunosewoyo, Hendra Yang, Fan Tang, Jie Pang, Tao Yu, Li-Fang Molecules Article Sigma-1 (σ-1) receptor agonists are considered as potential treatment for stroke. TS-157 is an alkoxyisoxazole-based σ-1 receptor agonist previously discovered in our group. The present study describes TS-157 profile in a battery of tests for cerebral ischemia. Initial evaluation demonstrated the compound’s safety profile and blood–brain barrier permeability, as well as its ability to induce neurite outgrowth in vitro. The neurite outgrowth was shown to be mediated via σ-1 receptor agonism and involves upregulation of ERK phosphorylation (pERK). In particular, TS-157 also significantly accelerated the recovery of motor function in rats with transient middle cerebral artery occlusion (tMCAO). Overall, the results herein support the notion that σ-1 receptor agonists are potential therapeutics for stroke and further animal efficacy studies are warranted. MDPI 2021-02-24 /pmc/articles/PMC7956808/ /pubmed/33668340 http://dx.doi.org/10.3390/molecules26051212 Text en © 2021 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Shi, Jun-Jie
Jiang, Qi-Hui
Zhang, Tian-Ning
Sun, Hao
Shi, Wen-Wen
Gunosewoyo, Hendra
Yang, Fan
Tang, Jie
Pang, Tao
Yu, Li-Fang
Sigma-1 Receptor Agonist TS-157 Improves Motor Functional Recovery by Promoting Neurite Outgrowth and pERK in Rats with Focal Cerebral Ischemia
title Sigma-1 Receptor Agonist TS-157 Improves Motor Functional Recovery by Promoting Neurite Outgrowth and pERK in Rats with Focal Cerebral Ischemia
title_full Sigma-1 Receptor Agonist TS-157 Improves Motor Functional Recovery by Promoting Neurite Outgrowth and pERK in Rats with Focal Cerebral Ischemia
title_fullStr Sigma-1 Receptor Agonist TS-157 Improves Motor Functional Recovery by Promoting Neurite Outgrowth and pERK in Rats with Focal Cerebral Ischemia
title_full_unstemmed Sigma-1 Receptor Agonist TS-157 Improves Motor Functional Recovery by Promoting Neurite Outgrowth and pERK in Rats with Focal Cerebral Ischemia
title_short Sigma-1 Receptor Agonist TS-157 Improves Motor Functional Recovery by Promoting Neurite Outgrowth and pERK in Rats with Focal Cerebral Ischemia
title_sort sigma-1 receptor agonist ts-157 improves motor functional recovery by promoting neurite outgrowth and perk in rats with focal cerebral ischemia
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7956808/
https://www.ncbi.nlm.nih.gov/pubmed/33668340
http://dx.doi.org/10.3390/molecules26051212
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