Sigma-1 受体激动剂 TS-157 通过促进局灶性脑缺血大鼠的神经突生长和 pERK 来改善运动功能恢复。
Sigma-1 Receptor Agonist TS-157 Improves Motor Functional Recovery by Promoting Neurite Outgrowth and pERK in Rats with Focal Cerebral Ischemia.
机构信息
Shanghai Engineering Research Center of Molecular Therapeutics and New Drug Development, School of Chemistry and Molecular Engineering, East China Normal University, 3663 North Zhongshan Road, Shanghai 200062, China.
New Drug Screening Center, Jiangsu Center for Pharmacodynamics Research and Evaluation, Institute of Pharmaceutical Sciences, China Pharmaceutical University, Nanjing 210009, China.
出版信息
Molecules. 2021 Feb 24;26(5):1212. doi: 10.3390/molecules26051212.
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.
西格玛-1（σ-1）受体激动剂被认为是治疗中风的潜在药物。TS-157 是我们小组先前发现的一种基于烷氧基异恶唑的 σ-1 受体激动剂。本研究描述了 TS-157 在一系列脑缺血测试中的概况。初步评估表明该化合物具有安全性和血脑屏障通透性，以及在体外诱导神经突生长的能力。神经突生长是通过 σ-1 受体激动作用介导的，并涉及 ERK 磷酸化（pERK）的上调。特别是，TS-157 还显著加速了短暂性大脑中动脉闭塞（tMCAO）大鼠运动功能的恢复。总的来说，这些结果支持了 σ-1 受体激动剂是治疗中风的潜在治疗方法的观点，需要进一步的动物疗效研究。
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