Dual role of Kisspeptin-10 in modulating neuroinflammation: Downregulation of NLRP3 inflammasome activation and Caspase-1-mediated pyroptosis, and activation of BAG3-dependent aggrephagy in microglial cells

Basit Öğe Kaydı
dc.contributor.authorKalkan, Omer Faruk
dc.contributor.authorErdem, Seniz
dc.contributor.authorErdem, Mehmet
dc.contributor.authorKalkan, Satinur Ateser
dc.contributor.authorSahin, Zafer
dc.contributor.authorUzun, Ali Yavuz
dc.contributor.authorKarahan, Suleyman Caner
dc.date.accessioned2026-06-19T06:39:45Z
dc.date.available2026-06-19T06:39:45Z
dc.date.issued2026
dc.departmentMalatya Turgut Özal Üniversitesi
dc.description.abstractBackground: Microglial NLRP3 inflammasome activation plays a central role in the neuroinflammatory cascade that contributes to the pathogenesis of various neurodegenerative diseases. Activation of the canonical inflammasome pathway leads to caspase-1 activation, gasdermin D (GSDMD) cleavage, and pyroptotic cell death, along with the release of pro-inflammatory cytokines such as interleukin-1(3 (IL-1(3) and interleukin-18 (IL-18). Kisspeptin-10 (KP-10), a bioactive neuropeptide of the kisspeptin family, has been shown to exert regulatory effects on immune function; however, its role in neuroinflammation process remains unclear. In this study, we investigated the effects of KP-10 on LPS + ATP-induced NLRP3 inflammasome activation and pyroptotic signaling in murine microglial cells. Results: KP-10 treatment significantly reduced NLRP3 expression, inhibited cleavage of caspase-1 into its active p20 subunit, and decreased GSDMD cleavage into its pore-forming N-terminal fragment (GSDMD-N), indicating suppression of inflammasome-dependent pyroptosis. KP-10 also attenuated the secretion of IL-1(3 and IL-18, confirming functional inhibition of the inflammasome pathway. Mechanistically, KP-10 markedly upregulated Bcl-2-associated athanogene 3 (BAG3), a key co-chaperone involved in selective autophagy. Conclusion: These findings demonstrate that KP-10 suppresses microglial pyroptosis and neuroinflammatory signaling through dual mechanisms: inhibition of the NLRP3-caspase-1-GSDMD axis and activation of BAG3-dependent selective autophagy. This study identifies KP-10 as a novel modulator of microglial inflammasome activity and highlights its therapeutic potential for treating neuroinflammatory and neurodegenerative disorders.
dc.description.sponsorshipScientific Research Projects Coordination Unit of Karadeniz Technical University [THD-2024-16070]
dc.description.sponsorshipThis research was supported by Scientific Research Projects Coordination Unit of Karadeniz Technical University. Project number: THD-2024-16070.
dc.identifier.doi10.1016/j.npep.2025.102580
dc.identifier.issn0143-4179
dc.identifier.issn1532-2785
dc.identifier.pmid41380532
dc.identifier.scopus2-s2.0-105024233051
dc.identifier.scopusqualityQ2
dc.identifier.urihttps://doi.org/10.1016/j.npep.2025.102580
dc.identifier.urihttps://hdl.handle.net/20.500.12899/5766
dc.identifier.volume115
dc.identifier.wosWOS:001639672700001
dc.identifier.wosqualityQ3
dc.indekslendigikaynakWeb of Science
dc.indekslendigikaynakScopus
dc.indekslendigikaynakPubMed
dc.language.isoen
dc.publisherElsevier
dc.relation.ispartofNeuropeptides
dc.relation.publicationcategoryMakale - Uluslararası Hakemli Dergi - Kurum Öğretim Elemanı
dc.rightsinfo:eu-repo/semantics/closedAccess
dc.snmzKA_WOS_20260612
dc.subjectNeuroinflammation
dc.subjectKisspeptin-10
dc.subjectNlrp3 Inflammasome
dc.subjectBcl-2-Associated Athanogene 3
dc.subjectPyroptosis
dc.subjectAutophagy
dc.subjectMicroglia
dc.titleDual role of Kisspeptin-10 in modulating neuroinflammation: Downregulation of NLRP3 inflammasome activation and Caspase-1-mediated pyroptosis, and activation of BAG3-dependent aggrephagy in microglial cells
dc.typeArticle

Dosyalar

Koleksiyon

WoS İndeksli Yayınlar Koleksiyonu
PubMed İndeksli Yayınlar Koleksiyonu
Scopus İndeksli Yayınlar Koleksiyonu