{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,10]],"date-time":"2026-09-10T09:07:33Z","timestamp":1789031253152,"version":"build-2803163510"},"reference-count":79,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,9,10]],"date-time":"2026-09-10T00:00:00Z","timestamp":1788998400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Mol. Neurosci."],"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Spinal cord injury (SCI) initiates a secondary-injury cascade involving mitochondrial dysfunction, metal dyshomeostasis, neuroinflammation, and regulated cell death. Cuproptosis, a copper-dependent form of regulated cell death driven by lipoylated mitochondrial protein aggregation, has reframed copper dyshomeostasis as a potential molecular vulnerability rather than a passive trace-metal disturbance.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Main body<\/jats:title>\n                    <jats:p>This targeted narrative review critically synthesizes the FDX1\u2013lipoylation\u2013DLAT\/DLST cuproptosis pathway, copper trafficking and redistribution after SCI, and the evidence boundary between spinal cord ischemia\u2013reperfusion injury (SCIRI) and traumatic SCI. We evaluate two distinct but interacting regulatory layers: non-coding RNAs (ncRNAs), including microRNAs, long non-coding RNAs, circular RNAs, and extracellular-vesicle RNAs; and epigenetic regulation, including DNA methylation, histone modifications, and RNA modifications. Evidence is graded to distinguish established canonical biochemistry, the strongest direct preclinical mechanistic evidence in spinal-cord models, associative or hypothesis-generating traumatic-SCI evidence, non-SCI mechanistic validation, and testable hypotheses.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>At present the ncRNA\u2013epigenetics\u2013cuproptosis axis represents a molecular-neurobiological framework that still requires experimental validation rather than a clinically actionable pathway. The highest-priority next step is temporally and spatially resolved traumatic SCI validation that combines copper mapping, cell-type-specific cuproptosis execution assays, immune profiling, and genetic or pharmacological rescue experiments.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fnmol.2026.1885261","type":"journal-article","created":{"date-parts":[[2026,9,10]],"date-time":"2026-09-10T08:16:27Z","timestamp":1789028187000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Copper-regulated cell death after spinal cord injury: evidence boundaries for non-coding RNA, epigenetics and cuproptosis"],"prefix":"10.3389","volume":"19","author":[{"given":"Jun","family":"Tao","sequence":"first","affiliation":[{"name":"Department of Rehabilitation Medicine, Yibin Traditional Chinese Medicine Hospital, Yibin","place":["Sichuan, China"]},{"name":"SCATCM Key Laboratory of Traditional Chinese Medicine Health Products Research and Clinical Evaluation (Yibin Traditional Chinese Medicine Hospital), Yibin","place":["Sichuan, China"]},{"name":"Yibin Clinical Research Center for Traditional Chinese Medicine Health Products, Yibin","place":["Sichuan, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guobing","family":"Wang","sequence":"additional","affiliation":[{"name":"SCATCM Key Laboratory of Traditional Chinese Medicine Health Products Research and Clinical Evaluation (Yibin Traditional Chinese Medicine Hospital), Yibin","place":["Sichuan, China"]},{"name":"Yibin Clinical Research Center for Traditional Chinese Medicine Health Products, Yibin","place":["Sichuan, China"]},{"name":"Department of Pathology, Yibin Traditional Chinese Medicine Hospital, Yibin","place":["Sichuan, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guoying","family":"Jiang","sequence":"additional","affiliation":[{"name":"Department of Rehabilitation Medicine, Yibin Traditional Chinese Medicine Hospital, Yibin","place":["Sichuan, China"]},{"name":"SCATCM Key Laboratory of Traditional Chinese Medicine Health Products Research and Clinical Evaluation (Yibin Traditional Chinese Medicine Hospital), Yibin","place":["Sichuan, China"]},{"name":"Yibin Clinical Research Center for Traditional Chinese Medicine Health Products, Yibin","place":["Sichuan, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wenqi","family":"Feng","sequence":"additional","affiliation":[{"name":"Department of Rehabilitation Medicine, Yibin Traditional Chinese Medicine Hospital, Yibin","place":["Sichuan, China"]},{"name":"SCATCM Key Laboratory of Traditional Chinese Medicine Health Products Research and Clinical Evaluation (Yibin Traditional Chinese Medicine Hospital), Yibin","place":["Sichuan, China"]},{"name":"Yibin Clinical Research Center for Traditional Chinese Medicine Health Products, Yibin","place":["Sichuan, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,9,10]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"280","DOI":"10.1038\/nature24049","article-title":"RNA targeting with CRISPR-cas13.","volume":"550","author":"Abudayyeh","year":"2017","journal-title":"Nature"},{"key":"B2","doi-asserted-by":"publisher","first-page":"17018","DOI":"10.1038\/nrdp.2017.18","article-title":"Traumatic spinal cord injury.","volume":"3","author":"Ahuja","year":"2017","journal-title":"Nat Rev Dis. 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