{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,28]],"date-time":"2026-09-28T02:56:21Z","timestamp":1790564181190,"version":"4.1.0"},"reference-count":43,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2026,9,15]],"date-time":"2026-09-15T00:00:00Z","timestamp":1789430400000},"content-version":"vor","delay-in-days":14,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2026,9,1]],"date-time":"2026-09-01T00:00:00Z","timestamp":1788220800000},"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":["Eur J of Neuroscience"],"published-print":{"date-parts":[[2026,9]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>Spinal cord injury (SCI) is a devastating neurological condition with limited therapeutic options. Emerging evidence implicates ferroptosis, an iron\u2010dependent form of regulated cell death driven by lipid peroxidation, in secondary injury cascades following SCI. However, the molecular regulators linking mitochondrial quality control to ferroptosis in the injured spinal cord remain incompletely characterized. Here, through integrated bioinformatics analysis of the GEO dataset GSE155610 combined with ferroptosis gene screening and weighted gene co\u2010expression network analysis (WGCNA), we identified PPARGC1A (PGC\u20101a) as a hub gene at the intersection of ferroptosis and mitochondrial dysfunction. Clinical validation in a retrospective cohort of 186 acute SCI patients demonstrated that serum ferritin, PPARGC1A, and PPARg expression levels in spinal cord tissue were significantly associated with neurological prognosis. In\u00a0vitro, PPARGC1A overexpression in oxygen\u2013glucose deprivation\/reoxygenation (OGD\/R)\u2010treated SH\u2010SY5Y cells attenuated ferroptosis by reducing intracellular ferrous iron (Fe2+), lipid reactive oxygen species, and malondialdehyde while restoring glutathione levels and GPX4 expression. Mechanistically, PPARGC1A promoted PPARg nuclear translocation and upregulated CD36 and CPT1A transcription, while enhancing PINK1\/Parkin\u2010mediated mitophagy. These protective effects were abolished by PPARGC1A knockdown and partially reversed by PPARg agonism. In a rat contusion SCI model, AAV\u2010mediated PPARGC1A overexpression improved BBB locomotor scores, preserved spinal cord tissue architecture, and restored PPARg\/GPX4 expression and mitophagy markers in\u00a0vivo. Collectively, these findings reveal that the PPARGC1A\/PPARg axis orchestrates a lipid metabolism mitochondrial quality\u2010control network that protects against ferroptosis in SCI, positioning this pathway as a potential therapeutic target.<\/jats:p>","DOI":"10.1111\/ejn.70672","type":"journal-article","created":{"date-parts":[[2026,9,15]],"date-time":"2026-09-15T10:51:49Z","timestamp":1789469509000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["PPARGC1A Modulation Attenuates Ferroptosis\u2010Related Injury and Promotes Functional Recovery After Spinal Cord Injury: Potential Involvement of PPAR\u03b3 Signaling"],"prefix":"10.1111","volume":"64","author":[{"given":"Deli","family":"Wang","sequence":"first","affiliation":[{"name":"Department of Spine Surgery The Second Affiliated Hospital of Xi'an Jiaotong University  Xi'an Shaanxi China"},{"name":"Department of Rehabilitation Medicine Renmin Hospital, Hubei 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