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Over a hundred genes are currently linked to CMT with enrichment for activities in myelination, axon transport, and protein synthesis. Mutations in tRNA synthetases cause dominantly inherited forms of CMT, and animal models with CMT-linked mutations in these enzymes display defects in neuronal protein synthesis. Rescuing protein synthesis in CMT-mutant neurons could offer exciting therapeutic options beyond symptom management. To address this need, we expressed CMT-linked variants of tyrosyl-tRNA synthetase (YARS\u2013CMT) in primary mouse sensory neurons derived from both male and female embryos and evaluated impacts on protein synthesis and cell viability. YARS\u2013CMT expression reduced protein synthesis in these neurons prior to the onset of caspase-dependent axon degeneration and cell death. To determine how YARS\u2013CMT expression affects axon outgrowth, we dissociated and replated these neurons to stimulate axon regeneration. To our surprise, axonal regrowth occurred normally in replated YARS\u2013CMT neurons. Moreover, replating YARS\u2013CMT neurons rescued protein synthesis. Inhibiting mammalian target of rapamycin suppressed rescue of protein synthesis after replating, consistent with its significant role in protein synthesis during axon regeneration. These discoveries identify new avenues for augmenting protein synthesis in diseased neurons and restoring protein synthesis in CMT or other neurological disorders.<\/jats:p>","DOI":"10.1523\/eneuro.0337-25.2026","type":"journal-article","created":{"date-parts":[[2026,3,24]],"date-time":"2026-03-24T17:50:13Z","timestamp":1774374613000},"page":"ENEURO.0337-25.2026","update-policy":"https:\/\/doi.org\/10.1523\/eneuro.crossmarkpolicy","source":"Crossref","is-referenced-by-count":1,"title":["Replating Induces mTOR-Dependent Rescue of Protein Synthesis in Charcot\u2013Marie\u2013Tooth Diseased 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