{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,8]],"date-time":"2026-10-08T00:58:53Z","timestamp":1791421133895,"version":"4.3.3"},"reference-count":29,"publisher":"Wiley","issue":"16","license":[{"start":{"date-parts":[[2009,5,19]],"date-time":"2009-05-19T00:00:00Z","timestamp":1242691200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Glia"],"published-print":{"date-parts":[[2009,12]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>The ubiquitin\u2010proteasome system (UPS), lysosomes, and autophagy are essential protein degradation systems for the regulation of a variety of cellular physiological events including the cellular response to injury. It has recently been reported that the UPS and autophagy mediate the axonal degeneration caused by traumatic insults and the retrieval of nerve growth factors. In the peripheral nerves, axonal degeneration after injury is accompanied by myelin degradation, which is tightly related to the reactive changes of Schwann cells called dedifferentiation. In this study, we examined the role of the UPS, lysosomal proteases, and autophagy in the early phase of Wallerian degeneration of injured peripheral nerves. We found that nerve injury induced an increase in the ubiquitin conjugation and lysosomal\u2010associated membrane protein\u20101 expression within 1 day without any biochemical evidence for autophagy activation. Using an <jats:italic>ex vivo<\/jats:italic> explant culture of the sciatic nerve, we observed that inhibiting proteasomes or lysosomal serine proteases prevented myelin degradation, whereas this was not observed when inhibiting autophagy. Interestingly, proteasome inhibition, but not leupeptin, prevented Schwann cells from inducing dedifferentiation markers such as p75 nerve growth factor receptor and glial fibrillary acidic protein <jats:italic>in vitro<\/jats:italic> and <jats:italic>in vivo<\/jats:italic>. In addition, proteasome inhibitors induced cell cycle arrest and cellular process formation in cultured Schwann cells. Taken together, these findings indicate that the UPS plays a role in the phenotype changes of Schwann cells in response to nerve injury. \u00a9 2009 Wiley\u2010Liss, Inc.<\/jats:p>","DOI":"10.1002\/glia.20894","type":"journal-article","created":{"date-parts":[[2009,5,19]],"date-time":"2009-05-19T21:25:40Z","timestamp":1242768340000},"page":"1825-1834","source":"Crossref","is-referenced-by-count":55,"title":["Proteasome inhibition suppresses Schwann cell dedifferentiation <i>in vitro<\/i> and <i>in vivo<\/i>"],"prefix":"10.1002","volume":"57","author":[{"given":"Hyun Kyoung","family":"Lee","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yoon 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