The brain-derived neurotrophic factor mimetic 7,8-dihydroxyflavone mitigates NLRP3 inflammasome activation and GSDMD-mediated pyroptosis and enhances the negative regulatory pathways of pyroptosis in microglia

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dc.contributor.authorErdem, Mehmet
dc.contributor.authorErdem, Seniz
dc.contributor.authorKarahan, Suleyman Caner
dc.contributor.authorAlver, Ahmet
dc.contributor.authorKarabulut, Soner
dc.contributor.authorYildiz, Gokhan
dc.date.accessioned2026-06-19T06:39:49Z
dc.date.available2026-06-19T06:39:49Z
dc.date.issued2025
dc.departmentMalatya Turgut Özal Üniversitesi
dc.description.abstractMicroglia are resident immune cells of brain, which serves as a driver of the innate immunity within the central nervous system (CNS). The NOD-like receptor family pyrin domain-containing 3 (NLRP3) inflammasome is a multiprotein complex that is critical component of the innate immunity and hyperactivation of inflammasome under various conditions contributing to the pathogenesis of neurodegenerative diseases (NDs). 7,8-Dihydroxyflavone (7,8-DHF) have become the focus of attention in studies on NDs due to exert its neurotrophic effects in the CNS. Recent studies have shown encouraging outcomes targeting immune regulatory and neuroprotective properties. 7,8-DHF is a specific tropomyosin-related kinase receptor B (TrkB) agonist and bioavailable brainderived neurotrophic factor (BDNF) mimetic, which has immunomodulator properties in the CNS. In the present study, we researched the effects of BDNF mimetic 7,8-DHF on NLRP3 inflammasome activation, GSDMDmediated pyroptosis, NF-kappa B signaling, ESCRT-III-dependent plasma membrane repair, and selective autophagy in LPS plus ATP-induced murine N9 microglial cells. These findings demonstrated that BDNF mimetic 7,8-DHF significantly reduced NLRP3 inflammasome activation, decreased active caspase-1 the levels, inhibited secretion of proinflammatory cytokine IL-1 beta and IL-18 levels through the I kappa B alpha/NF-kappa B axis. Furthermore, we showed that BDNF mimetic 7,8-DHF activated selective autophagy and ESCRT-III-dependent plasma membrane repair, both of which play crucial roles in the negative regulation of NLRP3 inflammasome activation. Our study reveals that BDNF mimetic 7,8-DHF effectively prevents microglial NLRP3 inflammasome activation and GSDMD-mediated pyroptosis by inhibiting I kappa B alpha/NF-kappa B, promoting ESCRT-III-dependent plasma membrane repair and enhancing selective autophagy.
dc.identifier.doi10.1016/j.jneuroim.2025.578684
dc.identifier.issn0165-5728
dc.identifier.issn1872-8421
dc.identifier.orcid0000-0002-6714-3343
dc.identifier.orcid0000-0001-9969-4409
dc.identifier.pmid40638969
dc.identifier.scopus2-s2.0-105009920962
dc.identifier.scopusqualityQ1
dc.identifier.urihttps://doi.org/10.1016/j.jneuroim.2025.578684
dc.identifier.urihttps://hdl.handle.net/20.500.12899/5811
dc.identifier.volume406
dc.identifier.wosWOS:001532988600001
dc.identifier.wosqualityQ3
dc.indekslendigikaynakWeb of Science
dc.indekslendigikaynakScopus
dc.indekslendigikaynakPubMed
dc.language.isoen
dc.publisherElsevier
dc.relation.ispartofJournal of Neuroimmunology
dc.relation.publicationcategoryMakale - Uluslararası Hakemli Dergi - Kurum Öğretim Elemanı
dc.rightsinfo:eu-repo/semantics/closedAccess
dc.snmzKA_WOS_20260612
dc.subject8-Dihydroxyflavone
dc.subjectMicroglia
dc.subjectNlrp3 Inflammasome
dc.subjectPyroptosis
dc.subjectEscrt-Iii-Dependent Plasma Membrane Repair
dc.subjectSelective Autophagy
dc.titleThe brain-derived neurotrophic factor mimetic 7,8-dihydroxyflavone mitigates NLRP3 inflammasome activation and GSDMD-mediated pyroptosis and enhances the negative regulatory pathways of pyroptosis in microglia
dc.typeArticle

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