{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,13]],"date-time":"2026-09-13T03:59:40Z","timestamp":1789271980894,"version":"build-2803163510"},"reference-count":50,"publisher":"Wiley","issue":"8","license":[{"start":{"date-parts":[[2025,8,1]],"date-time":"2025-08-01T00:00:00Z","timestamp":1754006400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["J of Neuroscience Research"],"published-print":{"date-parts":[[2025,8]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>Ischemic stroke (IS) is a prevalent and serious neurological disorder, and is one of the major contributors to mortality and disability worldwide. The activation of autophagy and the inflammatory response following cerebral ischemia are crucial in the progression of IS. Protein phosphatase 1 regulatory subunit 15A (PPP1R15A), as a stress\u2010responsive protein, has been proven to be closely associated with autophagy. Nevertheless, the molecular mechanism of PPP1R15A in IS remains to be fully understood. Our study screened PPP1R15A as a candidate gene by bioinformatics analysis of the differentially expressed genes (DEGs) in IS and autophagy\u2010related genes (ARGs). Functionally, experiments uncovered that down\u2010regulation of PPP1R15A alleviated oxygen\u2013glucose deprivation\/reoxygenation (OGD\/R)\u2010mediated inhibition of cell viability and promotion of LDH release, cell apoptosis, autophagy, and inflammation in A172 and SH\u2010SY5Y cells. Simultaneously, silencing PPP1R15A ameliorated the IS progression in the middle cerebral artery occlusion and reperfusion (MCAO\/R) rat model. Furthermore, PPP1R15A activated the toll\u2010like receptor 4 (TLR4)\/nuclear factor kappa B (NF\u2010\u03baB) pathway in\u00a0vivo and in\u00a0vitro. Rescue experiments indicated that TLR4 inhibitors TAK\u2010242 and NF\u2010\u03baB inhibitors BAY\u201011\u20107082 effectively alleviated the malignant progression of IS mediated by overexpression of PPP1R15A. Our data illustrated that PPP1R15A promoted OGD\/R\u2010induced cytotoxicity, apoptosis, autophagy, and inflammation by activating the TLR4\/NF\u2010\u03baB pathway.<\/jats:p>","DOI":"10.1002\/jnr.70073","type":"journal-article","created":{"date-parts":[[2025,8,2]],"date-time":"2025-08-02T05:59:31Z","timestamp":1754114371000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["<scp>PPP1R15A<\/scp>\n                    Promotes Apoptosis, Autophagy, and Inflammatory Response to Exacerbate Ischemic Stroke Through Activation of\n                    <scp>TLR4<\/scp>\n                    \/\n                    <scp>NF<\/scp>\n                    \u2010\n                    <scp>\u03baB<\/scp>\n                    Pathway"],"prefix":"10.1002","volume":"103","author":[{"given":"Lijuan","family":"Liu","sequence":"first","affiliation":[{"name":"Department of Neurology II Aviation General Hospital  Beijing 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