{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,6]],"date-time":"2026-09-06T04:04:32Z","timestamp":1788667472331,"version":"build-2803163510"},"reference-count":54,"publisher":"SAGE Publications","issue":"10","license":[{"start":{"date-parts":[[2025,5,15]],"date-time":"2025-05-15T00:00:00Z","timestamp":1747267200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["J Cereb Blood Flow Metab"],"published-print":{"date-parts":[[2025,10]]},"abstract":"<jats:p>\n                    <jats:italic toggle=\"yes\">N<\/jats:italic>\n                    <jats:sup>6<\/jats:sup>\n                    -methyladenosine (m\n                    <jats:sup>6<\/jats:sup>\n                    A) is a critical epitranscriptomic regulator of neuronal function. Cerebral ischemia induces m\n                    <jats:sup>6<\/jats:sup>\n                    A hypermethylation due to decreased expression of m\n                    <jats:sup>6<\/jats:sup>\n                    A demethylase fat mass and obesity-associated (FTO) protein. Previously, we showed that cerebral overexpression of FTO with an adeno-associated virus (AAV) 9 protects the post-stroke brain. We presently evaluated the mechanistic basis for FTO-dependent m\n                    <jats:sup>6<\/jats:sup>\n                    A demethylation in post-ischemic neuroprotection using the mice transient middle cerebral artery occlusion model of experimental stroke. Based on the bioinformatic predictions and m\n                    <jats:sup>6<\/jats:sup>\n                    A abundance, pro-apoptotic transcription factor Jun proto-oncogene (c-Jun) with 19\u2009m\n                    <jats:sup>6<\/jats:sup>\n                    A sites was chosen as an exemplary target. FTO overexpression normalized the post-stroke m\n                    <jats:sup>6<\/jats:sup>\n                    A hypermethylation of c-Jun without altering its transcript levels. FTO-dependent m\n                    <jats:sup>6<\/jats:sup>\n                    A demethylation suppressed translation of c-Jun. Consequently, several c-Jun target genes are transcriptionally repressed, and the post-ischemic neuronal apoptosis is decelerated, as seen by decreased cleaved caspase-3 levels and TUNEL\n                    <jats:sup>+<\/jats:sup>\n                    neurons in the FTO AAV9 treated group compared to the control AAV9 treated group. Moreover, replenishing c-Jun precluded the FTO-mediated post-stroke neuroprotection and functional recovery. Collectively, this study demonstrated that the FTO\/m\n                    <jats:sup>6<\/jats:sup>\n                    A\/c-Jun axis ameliorates post-stroke neuronal apoptosis and brain damage, leading to better functional outcomes.\n                  <\/jats:p>","DOI":"10.1177\/0271678x251340808","type":"journal-article","created":{"date-parts":[[2025,5,15]],"date-time":"2025-05-15T04:36:13Z","timestamp":1747283773000},"page":"1877-1890","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":5,"title":["FTO promotes post-stroke neuroprotection by m\n                    <sup>6<\/sup>\n                    A demethylation of c-Jun"],"prefix":"10.1177","volume":"45","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0101-0417","authenticated-orcid":false,"given":"Anil K","family":"Chokkalla","sequence":"first","affiliation":[{"name":"Department of Neurological Surgery, University of Wisconsin, Madison, WI, USA"},{"name":"Cellular &amp; Molecular Pathology Graduate Program, University of Wisconsin, Madison, WI, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5634-5230","authenticated-orcid":false,"given":"Suresh L","family":"Mehta","sequence":"additional","affiliation":[{"name":"Department of Neurological Surgery, University of Wisconsin, Madison, WI, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6989-3412","authenticated-orcid":false,"given":"Soomin","family":"Jeong","sequence":"additional","affiliation":[{"name":"Department of Neurological Surgery, University of Wisconsin, Madison, WI, USA"},{"name":"Neuroscience Training Program, University of Wisconsin, Madison, WI, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hui-Lung","family":"Sun","sequence":"additional","affiliation":[{"name":"Department of Chemistry, The University of Chicago, Chicago, IL, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qing","family":"Dai","sequence":"additional","affiliation":[{"name":"Department of Chemistry, The University of Chicago, Chicago, IL, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Raghu","family":"Vemuganti","sequence":"additional","affiliation":[{"name":"Department of Neurological Surgery, University of Wisconsin, Madison, WI, USA"},{"name":"Cellular &amp; Molecular Pathology Graduate Program, University of Wisconsin, Madison, WI, USA"},{"name":"Neuroscience Training Program, University of Wisconsin, Madison, WI, USA"},{"name":"William S. 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