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001-es BibID:	BIBFORM130425
Első szerző:	Kecskés Szilvia (anatómus, neurobiológus)
Cím:	The impact of the novel [sigma]1 receptor ligand (S)-L1 on brain endothelial cells and cerebrovascular reactivity challenged by ischemia / Szilvia Kecskés, Mária Mészáros, Szabolcs Dvorácskó, Írisz Szabó, Gergő Porkoláb, Lilla Barna, András Harazin, Anikó Szecskó, Ákos Menyhárt, Ferenc Bari, Mária A. Deli, Botond Penke, Eszter Farkas, Szilvia Veszelka
Dátum:	2025
ISSN:	0014-2999
Megjegyzések:	Intracellular sigma-1 receptors ([sigma]1 receptors) have a versatile function through the regulation of lipid rafts, neuroreceptors and ion channels, and can influence signal transduction and neuronal plasticity. Since decreased activity of [sigma]1 receptors is a common pathological feature in the early stages of many neurological diseases, [sigma]1 receptor agonists may represent a promising therapeutic tool for the treatment of these disorders. In this study, we aimed to comprehensively investigate the potential protective effects of the novel synthetic [sigma]1 receptor agonist (S)-L1 against endothelial endoplasmic reticulum (ER) stress and cerebral ischemia. In binding affinity experiments, we showed that (S)-L1 has a high affinity and selectivity for ?1 receptor with virtually no affinity for any of the other receptors tested. Next, (S)-L1 exerted protection against endoplasmic reticulum stress in human brain endothelial cells, consistent with the localization of [sigma]1 receptors in endothelial cells. Furthermore, (S)-L1 penetration was demonstrated across the cell culture model of the blood-brain barrier, providing a rationale for neuronal action in addition to endothelial protection. Finally, (S)-L1 inhibited spreading depolarization, suppressed apoptosis and rescued astrocytes in a rat model of cerebral ischemia. Based on our results, (S)-L1 exerts a protective effect on both brain endothelial cells and neural tissue. Moreover, since these experiments revealed no affinity for serotonergic receptors, the compound holds promise as an adjuvant therapy for the treatment of cerebrovascular disease without potential psychedelic side effects.
Tárgyszavak:	Természettudományok Biológiai tudományok idegen nyelvű folyóiratközlemény külföldi lapban folyóiratcikk Sigma-1 receptor ligand Brain endothelial cells Blood-brain barrier Cerebral ischemia Neurovascular coupling Spreading depolarization
Megjelenés:	European Journal Of Pharmacology. - 1000 (2025), p. 1-10. -
További szerzők:	Mészáros Mária (1990-) (biológus) Dvorácskó Szabolcs Szabó Írisz Porkoláb Gergő Barna Lilla Harazin András Szecskó Anikó Menyhárt Ákos Bari Ferenc Deli Mária A. Penke Botond Farkas Eszter Veszelka Szilvia
Pályázati támogatás:	OTKA PD-138930 Egyéb
Internet cím:	Szerző által megadott URL DOI Intézményi repozitóriumban (DEA) tárolt változat
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