{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,28]],"date-time":"2026-07-28T12:15:44Z","timestamp":1785240944512,"version":"3.55.0"},"reference-count":66,"publisher":"American Association for the Advancement of Science (AAAS)","issue":"15","content-domain":{"domain":["www.science.org"],"crossmark-restriction":true},"short-container-title":["Sci. Adv."],"published-print":{"date-parts":[[2024,4,12]]},"abstract":"<jats:p>Myelination is essential for neuronal function and health. In peripheral nerves, &gt;100 causative mutations have been identified that cause Charcot-Marie-Tooth disease, a disorder that can affect myelin sheaths. Among these, a number of mutations are related to essential targets of the posttranslational modification neddylation, although how these lead to myelin defects is unclear. Here, we demonstrate that inhibiting neddylation leads to a notable absence of peripheral myelin and axonal loss both in developing and regenerating mouse nerves. Our data indicate that neddylation exerts a global influence on the complex transcriptional and posttranscriptional program by simultaneously regulating the expression and function of multiple essential myelination signals, including the master transcription factor EGR2 and the negative regulators c-Jun and Sox2, and inducing global secondary changes in downstream pathways, including the mTOR and YAP\/TAZ signaling pathways. This places neddylation as a critical regulator of myelination and delineates the potential pathogenic mechanisms involved in CMT mutations related to neddylation.<\/jats:p>","DOI":"10.1126\/sciadv.adm7600","type":"journal-article","created":{"date-parts":[[2024,4,12]],"date-time":"2024-04-12T17:58:21Z","timestamp":1712944701000},"update-policy":"https:\/\/doi.org\/10.34133\/aaas_crossmark","source":"Crossref","is-referenced-by-count":8,"title":["Neddylation orchestrates the complex transcriptional and posttranscriptional program that drives Schwann cell myelination"],"prefix":"10.1126","volume":"10","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7737-9341","authenticated-orcid":true,"given":"Paula","family":"Ayuso-Garc\u00eda","sequence":"first","affiliation":[{"name":"Gene Regulatory Control in Disease Laboratory, Center for Research in Molecular Medicine and Chronic Diseases (CIMUS), Instituto de Investigaci\u00f3n Sanitaria de Santiago de Compostela (IDIS), University of Santiago de Compostela, 15706 Santiago de Compostela, A Coru\u00f1a, Spain."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4477-4959","authenticated-orcid":true,"given":"Alejandro","family":"S\u00e1nchez-Rueda","sequence":"additional","affiliation":[{"name":"Gene Regulatory Control in Disease Laboratory, Center for Research in Molecular Medicine and Chronic Diseases (CIMUS), Instituto de Investigaci\u00f3n Sanitaria de Santiago de Compostela (IDIS), University of Santiago de Compostela, 15706 Santiago de Compostela, A Coru\u00f1a, Spain."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9672-2264","authenticated-orcid":true,"given":"Sergio","family":"Velasco-Avil\u00e9s","sequence":"additional","affiliation":[{"name":"Gene Regulatory Control in Disease Laboratory, Center for Research in Molecular Medicine and Chronic Diseases (CIMUS), Instituto de Investigaci\u00f3n Sanitaria de Santiago de 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