{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,4]],"date-time":"2026-05-04T04:48:08Z","timestamp":1777870088188,"version":"3.51.4"},"reference-count":47,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2026,3,11]],"date-time":"2026-03-11T00:00:00Z","timestamp":1773187200000},"content-version":"vor","delay-in-days":10,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,3,1]],"date-time":"2026-03-01T00:00:00Z","timestamp":1772323200000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["CNS Neurosci Ther"],"published-print":{"date-parts":[[2026,3]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background and Objective<\/jats:title>\n                    <jats:p>Cerebral ischemia\u2013reperfusion injury (CIRI) is a major cause of poor outcome after ischemic stroke, and effective therapeutic targets are lacking. This study aimed to investigate the role of polypeptide N\u2010acetylgalactosaminyltransferase 3 (GALNT3) in CIRI.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>The mouse transient middle cerebral artery occlusion\/reperfusion (tMCAO\/R) model was established, and transcriptomic analysis of the peri\u2010infarct cortex was performed to screen target genes. In\u00a0vivo experiments, neurological scoring and TTC staining were used to assess the effects of GALNT3 on brain injury. In\u00a0vitro, microglial HMC3 cells subjected to oxygen\u2013glucose deprivation\/reoxygenation (OGD\/R) were used to model CIRI and further analyze the effects of GALNT3 on macrophage polarization and inflammatory factor expression.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Transcriptomic analysis of the peri\u2010infarct cortex in the tMCAO\/R model identified GALNT3 as a significantly down\u2010regulated gene. GALNT3 overexpression reduced infarct volume, improved neurological function, and suppressed neuronal apoptosis, oxidative stress, and neuroinflammation in tMCAO\/R mice. Subsequently, GALNT3 was further demonstrated to inhibit microglial M1 polarization and down\u2010regulate inflammatory factors in the OGD\/R model. Further mechanism investigation revealed that GALNT3, acting as a mucin type O glycosylation initiating enzyme, directly interacted with triggering receptor expressed on myeloid cells 2 (TREM2) and promoted its O GalNAc glycosylation, predominantly at serine 147, thereby enhancing TREM2 protein stability. TREM2 knockdown stimulated inflammatory responses that were inhibited by GALNT3 overexpression in OGD\/R\u2010treated microglia.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>This study revealed a novel GALNT3\/TREM2 regulatory axis that restricts neuroinflammation and injury after CIRI, highlighting GALNT3\u2010mediated O\u2010glycosylation as a potential therapeutic strategy for CIRI.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/cns.70828","type":"journal-article","created":{"date-parts":[[2026,3,12]],"date-time":"2026-03-12T04:49:16Z","timestamp":1773290956000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["<scp>GALNT3<\/scp>\n                    Inhibits the Progression of Cerebral Ischemia\u2013Reperfusion Injury by Stabilizing\n                    <scp>TREM2<\/scp>\n                    via O\u2010\n                    <scp>GalNAc<\/scp>\n                    Glycosylation"],"prefix":"10.1002","volume":"32","author":[{"given":"Xinyi","family":"Fei","sequence":"first","affiliation":[{"name":"Department of Neurology China\u2010Japan Union Hospital of Jilin University  Changchun Jilin China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jinghui","family":"Yang","sequence":"additional","affiliation":[{"name":"Department of Hepatobiliary and Pancreatic Surgery China\u2010Japan Union Hospital of Jilin University  Changchun Jilin China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rui","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Neurology China\u2010Japan Union Hospital of Jilin University  Changchun Jilin China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yu","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Neurology China\u2010Japan Union Hospital of 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