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Ubiquitination plays a crucial role in protein degradation, but its role in cerebral I\/R injury remains unclear. Differentially expressed genes in stroke were identified by analysing the microarray dataset GSE119121. Cerebral I\/R was simulated in vitro by treating human microglial HMC3 cells with oxygen\u2013glucose deprivation\/reperfusion (OGD\/R). Cell viability was tested by Cell Counting Kit 8 (CCK-8) assays, and pyroptosis was examined by flow cytometry. Lactate dehydrogenase (LDH) and inflammatory cytokine secretion were measured by LDH cytotoxicity assays and enzyme-linked immunosorbent assay (ELISA), respectively. The cerebral I\/R animal model was established by middle cerebral artery occlusion (MCAO) surgery in rats. Bioinformatic analysis indicated that tripartite motif-containing protein 59 (TRIM59) is downregulated in stroke, which was verified in cerebral I\/R models. The upregulation of TRIM59 promoted viability and inhibited pyroptosis in OGD\/R-treated microglia and alleviated cerebral I\/R injury in vivo. TRIM59 attenuated NOD-like receptor family pyrin domain containing 3 (NLRP3) protein expression through ubiquitination, thus degrading NLRP3 and alleviating OGD\/R-induced injury. TRIM59 relieves cerebral I\/R injury in vivo and in vivo. Mechanistically, TRIM59 directly interacts with NLRP3 and inhibits NLRP3 through ubiquitination. Targeting the TRIM59\/NLRP3 signalling axis may be an effective therapeutic strategy for cerebral I\/R.<\/jats:p>","DOI":"10.1038\/s41598-024-52914-7","type":"journal-article","created":{"date-parts":[[2024,1,31]],"date-time":"2024-01-31T08:55:57Z","timestamp":1706691357000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":13,"title":["TRIM59 suppresses the brain ischaemia\/reperfusion injury and pyroptosis of microglial through mediating the ubiquitination of NLRP3"],"prefix":"10.1038","volume":"14","author":[{"given":"Liangtian","family":"Zhang","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gang","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ying","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2024,1,30]]},"reference":[{"key":"52914_CR1","doi-asserted-by":"publisher","first-page":"105933","DOI":"10.1016\/j.phrs.2021.105933","volume":"174","author":"C Li","year":"2021","unstructured":"Li, C. et al. 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