Disease Modeling and Therapeutic Strategies in CMT2A: State of the Art

Mol Neurobiol. 2019 Sep;56(9):6460-6471. doi: 10.1007/s12035-019-1533-2. Epub 2019 Mar 4.


Mitofusin 2 (MFN2) is a protein of the mitochondrial outer membrane that belongs to a family of highly conserved dynamin-related GTPases. It is implicated in several intracellular pathways; however, its main role is the regulation of mitochondrial dynamics, in particular mitochondrial fusion. Mutations in MFN2 are associated with Charcot-Marie-Tooth disease type 2A (CMT2A), a neurological disorder characterized by a wide spectrum of clinical features, primarily a motor sensory neuropathy. The cellular and molecular mechanisms by which MFN2 mutations lead to neuronal degeneration are largely unknown, and there is currently no cure for patients. Here, we present the most recent in vitro and in vivo models of CMT2A and the more promising therapeutic approaches under development. These models and therapies may represent relevant tools for the study and recovery of defective mitochondrial dynamics that seem to play a significant role in the pathogenesis of other more common neurodegenerative diseases.

Keywords: Charcot–Marie–Tooth disease type 2; Gene therapy; Hereditary neuropathies; Mitochondrial diseases; Mitofusin agonists; Mitofusin2; Molecular therapy.

Publication types

  • Review

MeSH terms

  • Animals
  • Charcot-Marie-Tooth Disease / genetics
  • Charcot-Marie-Tooth Disease / therapy*
  • Disease Models, Animal*
  • Humans
  • Outcome Assessment, Health Care
  • Prognosis

Supplementary concepts

  • Charcot-Marie-Tooth disease, Type 2A