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

Molecules (Basel, Switzerland) 2021 Feb 24

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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.

Citation

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. Sigma-1 Receptor Agonist TS-157 Improves Motor Functional Recovery by Promoting Neurite Outgrowth and pERK in Rats with Focal Cerebral Ischemia. Molecules (Basel, Switzerland). 2021 Feb 24;26(5)