{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,23]],"date-time":"2026-09-23T22:18:12Z","timestamp":1790201892160,"version":"4.1.0"},"reference-count":51,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2024,3,2]],"date-time":"2024-03-02T00:00:00Z","timestamp":1709337600000},"content-version":"vor","delay-in-days":1,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"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>Objectives<\/jats:title><jats:p>FTO is known to be involved in cerebral ischemia\/reperfusion (I\/R) injury. However, its related specific mechanisms during this condition warrant further investigations. This study aimed at exploring the impacts of FTO and the FYN\/DRP1 axis on mitochondrial fission, oxidative stress (OS), and ferroptosis in cerebral I\/R injury and the underlying mechanisms.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>The cerebral I\/R models were established in mice via the temporary middle cerebral artery occlusion\/reperfusion (tMCAO\/R) and hypoxia\/reoxygenation models were induced in mouse hippocampal neurons via oxygen\u2013glucose deprivation\/reoxygenation (OGD\/R). After the gain\u2010 and loss\u2010of\u2010function assays, related gene expression was detected, along with the examination of mitochondrial fission, OS\u2010 and ferroptosis\u2010related marker levels, neuronal degeneration and cerebral infarction, and cell viability and apoptosis. The binding of FTO to FYN, m6A modification levels of FYN, and the interaction between FYN and Drp1 were evaluated.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>FTO was downregulated and FYN was upregulated in tMCAO\/R mouse models and OGD\/R cell models. FTO overexpression inhibited mitochondrial fission, OS, and ferroptosis to suppress cerebral I\/R injury in mice, which was reversed by further overexpressing FYN. FTO overexpression also suppressed mitochondrial fission and ferroptosis to increase cell survival and inhibit cell apoptosis in OGD\/R cell models, which was aggravated by additionally inhibiting DRP1. FTO overexpression inhibited FYN expression via the m6A modification to inactive Drp1 signaling, thus reducing mitochondrial fission and ferroptosis and enhancing cell viability in cells.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>FTO overexpression suppressed FYN expression through m6A modification, thereby subduing Drp1 activity and relieving cerebral I\/R injury.<\/jats:p><\/jats:sec>","DOI":"10.1111\/cns.14636","type":"journal-article","created":{"date-parts":[[2024,3,2]],"date-time":"2024-03-02T15:44:22Z","timestamp":1709394262000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":30,"title":["Fat mass and obesity associated protein inhibits neuronal ferroptosis via the <scp>FYN<\/scp>\/Drp1 axis and alleviate cerebral ischemia\/reperfusion injury"],"prefix":"10.1111","volume":"30","author":[{"given":"Yi","family":"Zhang","sequence":"first","affiliation":[{"name":"Department of Emergency, Hunan Provincial People's Hospital The First Affiliated Hospital of Hunan Normal University  Changsha Hunan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xin","family":"Gong","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, Hunan Provincial People's Hospital The First Affiliated Hospital of Hunan Normal University  Changsha Hunan 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