{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,9]],"date-time":"2026-07-09T04:49:57Z","timestamp":1783572597544,"version":"3.55.0"},"reference-count":36,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2024,3,28]],"date-time":"2024-03-28T00:00:00Z","timestamp":1711584000000},"content-version":"vor","delay-in-days":27,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81771261"],"award-info":[{"award-number":["81771261"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82071305"],"award-info":[{"award-number":["82071305"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["CNS Neurosci Ther"],"published-print":{"date-parts":[[2024,3]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Aims<\/jats:title><jats:p>Neuroinflammation and pyroptosis are key mediators of cerebral ischemia\/reperfusion (I\/R) injury\u2010induced pathogenic cascades. BRCC3, the human homolog of BRCC36, is implicated in neurological disorders and plays a crucial role in neuroinflammation and pyroptosis. However, its effects and potential mechanisms in cerebral I\/R injury in mice are unclear.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Cellular localization of BRCC3 and the interaction between BRCC3 and NLRP6 were assessed. Middle cerebral artery occlusion\/reperfusion (MCAO) and oxygen\u2013glucose deprivation\/reoxygenation (OGD\/R) models were established in mice and HT22 cells, respectively, to simulate cerebral I\/R injury in\u00a0vivo and in\u00a0vitro.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>BRCC3 protein expression peaked 24\u2009h after MCAO and OGD\/R. BRCC3 knockdown reduced the inflammation and pyroptosis caused by cerebral I\/R injury and ameliorated neurological deficits in mice after MCAO. The effects of BRCC3 on inflammation and pyroptosis may be mediated by NLRP6 inflammasome activation. Moreover, both BRCC3 and its N\u2010 and C\u2010terminals interacted with NLRP6, and both BRCC3 and its terminals reduced NLRP6 ubiquitination. Additionally, BRCC3 affected the interaction between NLRP6 and ASC, which may be related to inflammasome activation.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>BRCC3 shows promise as a novel target to enhance neurological recovery and attenuate the inflammatory responses and pyroptosis caused by NLRP6 activation in cerebral I\/R injury.<\/jats:p><\/jats:sec>","DOI":"10.1111\/cns.14697","type":"journal-article","created":{"date-parts":[[2024,3,28]],"date-time":"2024-03-28T07:21:35Z","timestamp":1711610495000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":24,"title":["<scp>BRCC3<\/scp> mediates inflammation and pyroptosis in cerebral ischemia\/reperfusion injury by activating the <scp>NLRP6<\/scp> inflammasome"],"prefix":"10.1111","volume":"30","author":[{"ORCID":"https:\/\/orcid.org\/0009-0006-5223-1320","authenticated-orcid":false,"given":"Xiaohuan","family":"Huang","sequence":"first","affiliation":[{"name":"Department of Pathology Chongqing Medical University  Chongqing China"},{"name":"Department of Pathology Chongqing Three Gorges Medical College  Wanzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Junyi","family":"Tan","sequence":"additional","affiliation":[{"name":"Department of Pathophysiology Chongqing Medical University  Chongqing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yanyan","family":"Ji","sequence":"additional","affiliation":[{"name":"Department of Pathology Chongqing Medical University  Chongqing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jing","family":"Luo","sequence":"additional","affiliation":[{"name":"Department of Pathology Chongqing Medical University  Chongqing 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