{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,10]],"date-time":"2026-09-10T12:22:16Z","timestamp":1789042936233,"version":"build-2803163510"},"reference-count":31,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2020,3,13]],"date-time":"2020-03-13T00:00:00Z","timestamp":1584057600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100003787","name":"Natural Science Foundation of Hebei Province","doi-asserted-by":"publisher","award":["H2017405021"],"award-info":[{"award-number":["H2017405021"]}],"id":[{"id":"10.13039\/501100003787","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Journal of Neurochemistry"],"published-print":{"date-parts":[[2021,3]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:label\/><jats:p>Necrostatin\u20101 (Nec\u20101) has previously been shown to protect neurons from death in traumatic and ischemic brain injuries. This study tests the hypothesis that Nec\u20101 protects neural cells against traumatic and ischemic brain injuries through inhibition of the Bcl\u20102\/adenovirus E1B 19\u2010kDa interacting protein 3 (BNIP3). We have used biochemical and morphological techniques to determine the inhibition of Nec\u20101 on BNIP3\u2010induced cell death and to identify its mechanism of action in in vivo and in vitro models of neurodegeneration. Here we show that Nec\u20101 significantly increased neuronal viability following prolonged exposure to hypoxia in vitro, and attenuated myelin damage and neuronal death in traumatic brain injury and cerebral ischemia in Sprague\u2010Dawley rats. Nec\u20101 alleviated traumatic brain injury\u2010induced up\u2010regulation of BNIP3 in mature oligodendrocytes. In isolated mitochondria, Nec\u20101 prevented BNIP3 from integrating into mitochondria by modifying its binding sites on the mitochondria. Consequently, Nec\u20101 robustly inhibited BNIP3\u2010induced collapse of mitochondrial membrane potential and reduced the opening probability of mitochondrial permeability transition pores. Nec\u20101 also preserved mitochondrial ultrastructure and suppressed BNIP3\u2010induced nuclear translocation of apoptosis\u2010inducing factor. In conclusion, Nec\u20101 protects neurons and oligodendrocytes against traumatic and ischemic brain injuries by targeting the BNIP3\u2010induced cell death pathway, and is a novel inhibitor for BNIP3.<\/jats:p><\/jats:sec><jats:sec><jats:label\/><jats:p>\n<jats:boxed-text content-type=\"graphic\" position=\"anchor\"><jats:graphic xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" mimetype=\"image\/png\" position=\"anchor\" specific-use=\"enlarged-web-image\" xlink:href=\"graphic\/jnc14993-fig-0010-m.png\"><jats:alt-text>image<\/jats:alt-text><\/jats:graphic><\/jats:boxed-text>\n<\/jats:p><jats:p><jats:bold>Cover Image for this issue:<\/jats:bold>\u00a0<jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" xlink:href=\"https:\/\/doi.org\/10.1111\/jnc.15056\">https:\/\/doi.org\/10.1111\/jnc.15056<\/jats:ext-link>.<\/jats:p><\/jats:sec>","DOI":"10.1111\/jnc.14993","type":"journal-article","created":{"date-parts":[[2020,2,29]],"date-time":"2020-02-29T09:30:07Z","timestamp":1582968607000},"page":"929-942","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":15,"title":["Necrostatin\u20101 prevents the proapoptotic protein Bcl\u20102\/adenovirus E1B 19\u2010kDa interacting protein 3 from integration into mitochondria"],"prefix":"10.1111","volume":"156","author":[{"given":"Jiao","family":"Mu","sequence":"first","affiliation":[{"name":"Department of Forensic Medicine Hebei North University Zhangjiakou China"},{"name":"Department of Human Anatomy and Cell Science Rady Faculty of Health Sciences Max Rady College of Medicine University of Manitoba Winnipeg Manitoba 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