Replating induces mTOR-dependent rescue of protein synthesis in Charcot-Marie-Tooth diseased neurons.

ABSTRACT: Charcot-Marie-Tooth disease (CMT) is an inherited peripheral neuropathy characterized by sensory dysfunction and muscle weakness, manifesting in the most distal limbs first and progressing more proximal. 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 in tyrosyl tRNA synthetase (YARS-CMT) in primary sensory neurons and evaluated impacts on protein synthesis and

SUBMITTER: Koenig J 

PROVIDER: S-EPMC12407962 | biostudies-literature | 2025 Aug

REPOSITORIES: biostudies-literature