{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T09:17:05Z","timestamp":1785403025895,"version":"3.56.0"},"reference-count":72,"publisher":"eLife Sciences Publications, Ltd","license":[{"start":{"date-parts":[[2023,10,17]],"date-time":"2023-10-17T00:00:00Z","timestamp":1697500800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2023,10,17]],"date-time":"2023-10-17T00:00:00Z","timestamp":1697500800000},"content-version":"am","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2023,10,17]],"date-time":"2023-10-17T00:00:00Z","timestamp":1697500800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100002347","name":"Bundesministerium f\u00fcr Bildung und Forschung","doi-asserted-by":"crossref","award":["03VP05200"],"award-info":[{"award-number":["03VP05200"]}],"id":[{"id":"10.13039\/501100002347","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":["elifesciences.org"],"crossmark-restriction":false},"short-container-title":[],"abstract":"<jats:p>\n                    Injured axons in the central nervous system (CNS) usually fail to regenerate, causing permanent disabilities. However, the knockdown of\n                    <jats:italic>Pten<\/jats:italic>\n                    knockout or treatment of neurons with hyper-IL-6 (hIL-6) transforms neurons into a regenerative state, allowing them to regenerate axons in the injured optic nerve and spinal cord. Transneuronal delivery of hIL-6 to the injured brain stem neurons enables functional recovery after severe spinal cord injury. Here we demonstrate that the beneficial hIL-6 and\n                    <jats:italic>Pten<\/jats:italic>\n                    knockout effects on axon growth are limited by the induction of tubulin detyrosination in axonal growth cones. Hence, cotreatment with parthenolide, a compound blocking microtubule detyrosination, synergistically accelerates neurite growth of cultured murine CNS neurons and primary RGCs isolated from adult human eyes. Systemic application of the prodrug dimethylamino-parthenolide (DMAPT) facilitates axon regeneration in the injured optic nerve and spinal cord. Moreover, combinatorial treatment further improves hIL-6-induced axon regeneration and locomotor recovery after severe SCI. Thus, DMAPT facilitates functional CNS regeneration and reduces the limiting effects of pro-regenerative treatments, making it a promising drug candidate for treating CNS injuries.\n                  <\/jats:p>","DOI":"10.7554\/elife.88279","type":"journal-article","created":{"date-parts":[[2023,7,5]],"date-time":"2023-07-05T11:46:41Z","timestamp":1688557601000},"update-policy":"https:\/\/doi.org\/10.7554\/elife.88279","source":"Crossref","is-referenced-by-count":7,"title":["Inhibition of microtubule detyrosination by parthenolide facilitates functional CNS axon regeneration"],"prefix":"10.7554","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6618-324X","authenticated-orcid":true,"given":"Marco","family":"Leibinger","sequence":"first","affiliation":[{"id":[{"id":"https:\/\/ror.org\/00rcxh774","id-type":"ROR","asserted-by":"publisher"}],"name":"Center for Pharmacology, Institute II, Medical Faculty and University of Cologne","place":["Cologne, 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