{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,20]],"date-time":"2026-07-20T17:08:04Z","timestamp":1784567284449,"version":"3.55.0"},"reference-count":25,"publisher":"Oxford University Press (OUP)","license":[{"start":{"date-parts":[[2026,7,20]],"date-time":"2026-07-20T00:00:00Z","timestamp":1784505600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"funder":[{"name":"Shenzhen Society of Health Economics","award":["202539"],"award-info":[{"award-number":["202539"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Ferroptosis has a crucial role in cerebral ischemia-reperfusion injury (IRI) but its potential modulation is a key challenge in the treatment of ischemic stroke. The function and mechanism of the E3 ubiquitin ligase tripartite motif-containing protein 21 (TRIM21) in neurological diseases, particularly its regulatory role in ferroptosis are unclear. We used a mouse model of transient middle cerebral artery occlusion (tMCAO\/R) and a PC12 cell model of oxygen-glucose deprivation\/reperfusion (OGD\/R) to investigate the effects of virus-mediated gene knockdown of TRIM21. Effects were assessed using Western blotting, immunoprecipitation, biochemical assays, and behavioral tests. TRIM21 expression was significantly increased after cerebral IRI. Knockdown of TRIM21 improved neurological deficits, reduced cerebral infarct size, and suppressed inflammation. Knockdown of TRIM21 also inhibited ferroptosis and improved mitochondrial function whereas TRIM21 negatively regulated the p62-Keap1-Nrf2 pathway through ubiquitination of p62. Salvage experiments confirmed that Nrf2 is a key downstream molecule for the neuroprotective effects of TRIM21. The data indicate that TRIM21 inhibition of the Keap1-Nrf2 pathway through p62 ubiquitination exacerbated ferroptosis after ischemic stroke in the tMCAO\/R model and suggest that targeted inhibition of TRIM21 holds promise as a novel strategy for treating ischemic stroke.<\/jats:p>","DOI":"10.1093\/jnen\/nlag075","type":"journal-article","created":{"date-parts":[[2026,7,20]],"date-time":"2026-07-20T16:51:54Z","timestamp":1784566314000},"source":"Crossref","is-referenced-by-count":0,"title":["Knockdown of TRIM21 inhibits ferroptosis via the p62-Keap1-Nrf2 pathway thereby improving brain injury and mitochondrial dysfunction after ischemia-reperfusion in mice"],"prefix":"10.1093","author":[{"given":"Bo","family":"Yang","sequence":"first","affiliation":[{"name":"Department of Neurosurgery, People\u2019s Hospital of Longhua District Shenzhen City , Shenzhen, Guangdong,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yanxia","family":"Sun","sequence":"additional","affiliation":[{"name":"Department of Cardiovascular Medicine, People\u2019s Hospital of Longhua District Shenzhen City , Shenzhen, Guangdong,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yao","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Sport Medicine, People\u2019s Hospital of Longhua District Shenzhen City , Shenzhen, Guangdong,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yanli","family":"Gu","sequence":"additional","affiliation":[{"name":"Central Laboratory, People\u2019s Hospital of Longhua District Shenzhen City , Shenzhen, Guangdong,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zheng","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, People\u2019s 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