Sigma-1 Receptor Agonist TS-157 Improves Motor Functional Recovery by Promoting Neurite Outgrowth and pERK in Rats with Focal Cerebral Ischemia.
Animals
Extracellular Signal-Regulated MAP Kinases
/ metabolism
Infarction, Middle Cerebral Artery
/ drug therapy
Male
Molecular Structure
Motor Activity
/ drug effects
Neuronal Outgrowth
/ drug effects
Oxazoles
/ chemical synthesis
Phosphorylation
/ drug effects
Rats
Rats, Sprague-Dawley
Receptors, sigma
/ agonists
Recovery of Function
/ drug effects
Sigma-1 Receptor
TS-157
focal cerebral ischemia
neurite outgrowth
pERK
sigma-1 receptor
Journal
Molecules (Basel, Switzerland)
ISSN: 1420-3049
Titre abrégé: Molecules
Pays: Switzerland
ID NLM: 100964009
Informations de publication
Date de publication:
24 Feb 2021
24 Feb 2021
Historique:
received:
13
01
2021
revised:
20
02
2021
accepted:
21
02
2021
entrez:
6
3
2021
pubmed:
7
3
2021
medline:
10
4
2021
Statut:
epublish
Résumé
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.
Identifiants
pubmed: 33668340
pii: molecules26051212
doi: 10.3390/molecules26051212
pmc: PMC7956808
pii:
doi:
Substances chimiques
Oxazoles
0
Receptors, sigma
0
Extracellular Signal-Regulated MAP Kinases
EC 2.7.11.24
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Subventions
Organisme : National Natural Science Foundation of China
ID : 81402780, 81973512
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