Sigma-1 receptor agonist TS-157 improves motor functional recovery by promoting neurite outgrowth and pERK in rats with focal cerebral ischemia

Jun Jie Shi; Qi Hui Jiang; Tian Ning Zhang; Hao Sun; Wen Wen Shi; Hendra Gunosewoyo; Fan Yang; Jie Tang; Tao Pang; Li Fang Yu

doi:10.3390/molecules26051212

Sigma-1 receptor agonist TS-157 improves motor functional recovery by promoting neurite outgrowth and pERK in rats with focal cerebral ischemia

Jun Jie Shi, Qi Hui Jiang, Tian Ning Zhang, Hao Sun, Wen Wen Shi, Hendra Gunosewoyo, Fan Yang, Jie Tang, Tao Pang, Li Fang Yu

School of Chemistry and Molecular Engineering

Research output: Contribution to journal › Article › peer-review

8 Scopus citations

Abstract

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.

Original language	English
Article number	1212
Journal	Molecules
Volume	26
Issue number	5
DOIs	https://doi.org/10.3390/molecules26051212
State	Published - 1 Mar 2021

Keywords

Focal cerebral ischemia
Neurite outgrowth
Sigma-1 receptor
TS-157
pERK

Access to Document

10.3390/molecules26051212

Cite this

@article{56d72c12052c459685674ca18f407747,

title = "Sigma-1 receptor agonist TS-157 improves motor functional recovery by promoting neurite outgrowth and pERK in rats with focal cerebral ischemia",

abstract = "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{\textquoteright}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.",

keywords = "Focal cerebral ischemia, Neurite outgrowth, Sigma-1 receptor, TS-157, pERK",

author = "Shi, \{Jun Jie\} and Jiang, \{Qi Hui\} and Zhang, \{Tian Ning\} and Hao Sun and Shi, \{Wen Wen\} and Hendra Gunosewoyo and Fan Yang and Jie Tang and Tao Pang and Yu, \{Li Fang\}",

note = "Publisher Copyright: {\textcopyright} 2021 by the authors.",

year = "2021",

month = mar,

day = "1",

doi = "10.3390/molecules26051212",

language = "英语",

volume = "26",

journal = "Molecules",

issn = "1420-3049",

publisher = "Multidisciplinary Digital Publishing Institute (MDPI)",

number = "5",

}

TY - JOUR

T1 - Sigma-1 receptor agonist TS-157 improves motor functional recovery by promoting neurite outgrowth and pERK in rats with focal cerebral ischemia

AU - Shi, Jun Jie

AU - Jiang, Qi Hui

AU - Zhang, Tian Ning

AU - Sun, Hao

AU - Shi, Wen Wen

AU - Gunosewoyo, Hendra

AU - Yang, Fan

AU - Tang, Jie

AU - Pang, Tao

AU - Yu, Li Fang

PY - 2021/3/1

Y1 - 2021/3/1

N2 - 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.

AB - 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.

KW - Focal cerebral ischemia

KW - Neurite outgrowth

KW - Sigma-1 receptor

KW - TS-157

KW - pERK

UR - https://www.scopus.com/pages/publications/85102713194

U2 - 10.3390/molecules26051212

DO - 10.3390/molecules26051212

M3 - 文章

C2 - 33668340

AN - SCOPUS:85102713194

SN - 1420-3049

VL - 26

JO - Molecules

JF - Molecules

IS - 5

M1 - 1212

ER -

Sigma-1 receptor agonist TS-157 improves motor functional recovery by promoting neurite outgrowth and pERK in rats with focal cerebral ischemia

Abstract

Keywords

Access to Document

Other files and links

Fingerprint

Cite this