{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,30]],"date-time":"2026-08-30T20:24:25Z","timestamp":1788121465578,"version":"build-2803163510"},"reference-count":33,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2024,4,26]],"date-time":"2024-04-26T00:00:00Z","timestamp":1714089600000},"content-version":"vor","delay-in-days":25,"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":[[2024,4]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Aims<\/jats:title><jats:p>Excessive neuroinflammation mediated mainly by microglia plays a crucial role in ischemic stroke. AZD1390, an ataxia telangiectasia mutated (ATM) specific inhibitor, has been shown to promote radio\u2010sensitization and survival in central nervous system malignancies, while the role of AZD1390 in ischemic stroke remains unknown.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Real\u2010time PCR, western blot, immunofluorescence staining, flow cytometry and enzyme\u2010linked immunosorbent assays were used to assess the activation of microglia and the release of inflammatory cytokines. Behavioral tests were performed to measure neurological deficits. 2,3,5\u2010Triphenyltetrazolium chloride staining was conducted to assess the infarct volume. The activation of NF\u2010\u03baB signaling pathway was explored through immunofluorescence staining, western blot, co\u2010immunoprecipitation and proximity ligation assay.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>The level of pro\u2010inflammation cytokines and activation of NF\u2010\u03baB signaling pathway was suppressed by AZD1390 in\u00a0vitro and in\u00a0vivo. The behavior deficits and infarct size were partially restored with AZD1390 treatment in experimental stroke. AZD1390 restrict ubiquitylation and sumoylation of the essential regulatory subunit of NF\u2010\u03baB (NEMO) in an ATM\u2010dependent and ATM\u2010independent way respectively, which reduced the activation of the NF\u2010\u03baB pathway.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>AZD1390 suppressed NF\u2010\u03baB signaling pathway to alleviate ischemic brain injury in experimental stroke, and attenuated microglia activation and neuroinflammation, which indicated that AZD1390 might be an attractive agent for the treatment of ischemic stroke.<\/jats:p><\/jats:sec>","DOI":"10.1111\/cns.14696","type":"journal-article","created":{"date-parts":[[2024,4,26]],"date-time":"2024-04-26T14:39:43Z","timestamp":1714142383000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["<scp>AZD<\/scp>1390, an ataxia telangiectasia mutated inhibitor, attenuates microglia\u2010mediated neuroinflammation and 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