Sigma-1 Receptor Agonist TS-157 Improves Motor Functional Recovery by Promoting Neurite Outgrowth and pERK in Rats with Focal Cerebral Ischemia.
Jun-Jie ShiQi-Hui JiangTian-Ning ZhangHao SunWen-Wen ShiHendra GunosewoyoFan YangJie TangTao PangLi-Fang YuPublished in: Molecules (Basel, Switzerland) (2021)
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.
Keyphrases
- cerebral ischemia
- blood brain barrier
- middle cerebral artery
- subarachnoid hemorrhage
- brain injury
- endoplasmic reticulum stress
- signaling pathway
- cell proliferation
- internal carotid artery
- atrial fibrillation
- human health
- endothelial cells
- poor prognosis
- risk assessment
- combination therapy
- solid state
- case control
- replacement therapy
- binding protein
- smoking cessation