{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,28]],"date-time":"2026-08-28T19:22:52Z","timestamp":1787944972423,"version":"build-2784847793"},"reference-count":48,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2026,2,17]],"date-time":"2026-02-17T00:00:00Z","timestamp":1771286400000},"content-version":"vor","delay-in-days":16,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,2,1]],"date-time":"2026-02-01T00:00:00Z","timestamp":1769904000000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100017594","name":"Medical Science and Technology Project of Zhejiang Province","doi-asserted-by":"publisher","award":["2023KY349"],"award-info":[{"award-number":["2023KY349"]}],"id":[{"id":"10.13039\/501100017594","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100017594","name":"Medical Science and Technology Project of Zhejiang Province","doi-asserted-by":"publisher","award":["2023KY359"],"award-info":[{"award-number":["2023KY359"]}],"id":[{"id":"10.13039\/501100017594","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["CNS Neurosci Ther"],"published-print":{"date-parts":[[2026,2]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>After spinal cord injury (SCI), neuronal lipid peroxidation and excessive production of reactive oxygen species (ROS) induced by secondary injury exacerbate ferroptosis, impeding regenerative repair and functional recovery in mice. Thus, clarifying the molecular and cellular mechanisms underlying the inhibition of neuronal ferroptosis post\u2010SCI is crucial.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Single\u2010cell RNA sequencing (scRNA\u2010seq) and single\u2010cell assay for transposase\u2010accessible chromatin sequencing (scATAC\u2010seq) were used to analyze changes in the transcription factor CREB5 post\u2010SCI. Combined with in\u00a0vitro (primary neuron experiments) and in\u00a0vivo (mouse SCI model) studies, CREB5 was knocked down\/overexpressed, and ApoL6 was overexpressed. Indicators related to neuronal ferroptosis (ROS, lipid peroxidation, free fatty acids, etc.) and functional recovery in mice were detected.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>After SCI, the transcriptional activity of the transcription factor CREB5 is enhanced, and its expression level first increases and then decreases. Mechanistically, CREB5 inhibits the decomposition of neuronal lipid droplets (LDs) by enhancing the transcriptional activity of the lipolysis\u2010related protein ApoL6, reducing the release of free fatty acids (FFA) and fatty acid oxidation (FAO), thereby decreasing ROS generation and lipid peroxidation, and ultimately inhibiting neuronal ferroptosis. In\u00a0vitro experiments showed that CREB5 knockdown exacerbates neuronal death and inhibits axonal growth; in\u00a0vivo experiments demonstrated that CREB5 knockdown hinders axonal growth and functional recovery in mice post\u2010SCI, while ApoL6 overexpression partially reverses these impairments.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>CREB5 maintains the balance of neuronal lipid droplet metabolism by regulating ApoL6 and serves as a potential therapeutic target for inhibiting neuronal ferroptosis after SCI.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/cns.70783","type":"journal-article","created":{"date-parts":[[2026,2,17]],"date-time":"2026-02-17T10:20:24Z","timestamp":1771323624000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["<scp>CREB5<\/scp>\n                    Inhibits Neuronal Ferroptosis via Transactivating\n                    <scp>ApoL6<\/scp>\n                    to Regulate Lipid Droplet Metabolism After Spinal Cord Injury"],"prefix":"10.1002","volume":"32","author":[{"given":"Xiaolong","family":"Xi","sequence":"first","affiliation":[{"name":"Department of Surgical Critical Care Medicine Shaoxing People's Hospital  Shaoxing Zhejiang China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhensen","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Surgical Critical Care Medicine Shaoxing People's Hospital  Shaoxing Zhejiang China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chaojun","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Surgical Critical Care Medicine Shaoxing People's Hospital  Shaoxing Zhejiang 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