R 2-adrenoceptor agonist formoterol attenuates NLRP3 inflammasome activation and GSDMD-mediated pyroptosis in microglia through enhancing IκBα/NF-κB κ B α /NF- κ B inhibition, SQSTM1/p62-dependent selective autophagy and ESCRT-III-mediated plasma membrane repair

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dc.contributor.authorErdem, Mehmet
dc.contributor.authorErdem, Seniz
dc.contributor.authorAlver, Ahmet
dc.contributor.authorKiran, Tugba Raika
dc.contributor.authorKarahan, Sueleyman Caner
dc.date.accessioned2026-06-19T06:39:47Z
dc.date.available2026-06-19T06:39:47Z
dc.date.issued2024
dc.departmentMalatya Turgut Özal Üniversitesi
dc.description.abstractMicroglia are immune cells that play important roles in the formation of the innate immune response within the central nervous system (CNS). The NOD-like receptor family pyrin domain-containing 3 (NLRP3) inflammasome is a multiple protein complex that is crucial for innate immunity, and excessive activation of the inflammasome for various reasons contributes to the pathogenesis of neurodegenerative diseases (NDs). R2-adrenoceptor 2-adrenoceptor agonists have become the focus of attention in studies on NDs due to the high synthesis of R2-adrenoceptors 2-adrenoceptors in the central nervous system (CNS). Promising results have been obtained from these studies targeting antiinflammatory and neuroprotective effects. Formoterol is an effective, safe for long-term use, and FDA- approved R2-adrenoceptor 2-adrenoceptor agonist with demonstrated anti-inflammatory features in the CNS. In this study, we researched the effects of formoterol on LPS/ATP-stimulated NLRP3 inflammasome activation, pyroptosis, NF-kappa B, autophagy, and ESCRT-III-mediated plasma membrane repair pathways in the N9 microglia cells. The results showed that formoterol, through the I kappa B alpha/NF-kappa B axis, significantly inhibited NLRP3 inflammasome activation, reduced the level of active caspase-1, secretion of IL-1R and IL-18 proinflammatory cytokine levels, and the levels of pyroptosis. Additionally, we showed that formoterol activates autophagy, autophagosome formation, and ESCRT-III-mediated plasma membrane repair, which are significant pathways in the inhibition of NLRP3 inflammasome activation and pyroptosis. Our study suggests that formoterol efficaciously prevents the NLRP3 inflammasome activation and pyroptosis in microglial cells regulation through I kappa B alpha/NF-kappa B, autophagy, autophagosome formation, and ESCRT-III-mediated plasma membrane repair.
dc.description.sponsorshipScientific Research Projects Coordination Unit of Karadeniz Technical University, Turkey [TDK-2022-10126, THD-2022-10150]
dc.description.sponsorshipThis study was supported by a grant from the Scientific Research Projects Coordination Unit of Karadeniz Technical University, Turkey [Grant numbers TDK-2022-10126 and THD-2022-10150] .
dc.identifier.doi10.1016/j.mcn.2024.103956
dc.identifier.issn1044-7431
dc.identifier.issn1095-9327
dc.identifier.orcid0000-0002-9100-2479
dc.identifier.orcid0000-0002-3724-0249
dc.identifier.orcid0000-0001-5643-3057
dc.identifier.orcid0000-0002-9617-6689
dc.identifier.pmid39097250
dc.identifier.scopus2-s2.0-85200152850
dc.identifier.scopusqualityQ3
dc.identifier.urihttps://doi.org/10.1016/j.mcn.2024.103956
dc.identifier.urihttps://hdl.handle.net/20.500.12899/5794
dc.identifier.volume130
dc.identifier.wosWOS:001289924500001
dc.identifier.wosqualityQ3
dc.indekslendigikaynakWeb of Science
dc.indekslendigikaynakScopus
dc.indekslendigikaynakPubMed
dc.language.isoen
dc.publisherAcademic Press Inc Elsevier Science
dc.relation.ispartofMolecular and Cellular Neuroscience
dc.relation.publicationcategoryMakale - Uluslararası Hakemli Dergi - Kurum Öğretim Elemanı
dc.rightsinfo:eu-repo/semantics/closedAccess
dc.snmzKA_WOS_20260612
dc.subjectFormoterol
dc.subjectMicroglia
dc.subjectNlrp3 Inflammasome
dc.subjectPyroptosis
dc.subjectAutophagy
dc.subjectEscrt-Iii-Mediated Plasma Membrane Repair
dc.titleR 2-adrenoceptor agonist formoterol attenuates NLRP3 inflammasome activation and GSDMD-mediated pyroptosis in microglia through enhancing IκBα/NF-κB κ B α /NF- κ B inhibition, SQSTM1/p62-dependent selective autophagy and ESCRT-III-mediated plasma membrane repair
dc.typeArticle

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