title: Charcot-Marie-Tooth disease: emerging mechanisms and therapies.
abstract: Charcot-Marie-Tooth disease is the most common inherited disorder of the peripheral nervous system. The disease is characterized by a progressive muscle weakness and atrophy, sensory loss, foot (and hand) deformities and steppage gait. While many of the genes associated with axonal CMT have been identified, to date it is unknown which mechanism(s) causes the disease. However, genetic findings indicate that the underlying mechanisms mainly converge to the axonal cytoskeleton. In this review, we will summarize the evidence for this pathogenic convergence. Furthermore, recent work with new transgenic mouse models has led to the identification of histone deacetylase 6 as a potential therapeutic target for inherited peripheral neuropathies. This enzyme deacetylates microtubules and plays a crucial role in the regulation of axonal transport. These findings offer new perspectives for a potential therapy to treat axonal Charcot-Marie-Tooth disease and other neurodegenerative disorders characterized by axonal transport defects.
authors.affiliation: Vesalius Research Center, VIB, Leuven, Belgium.
authors.forename: Constantin
authors.initials: C
authors.lastname: d'Ydewalle
authors.forename: Veronick
authors.initials: V
authors.lastname: Benoy
authors.forename: Ludo
authors.initials: L
authors.lastname: Van Den Bosch
mesh_terms: D000818:Animals; D001370:Axonal Transport / Q000235:genetics; D001369:Axons / Q000378:metabolism / Q000473:pathology; D002607:Charcot-Marie-Tooth Disease / Q000235:genetics* / Q000473:pathology / Q000628:therapy*; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D000073864:Histone Deacetylase 6; D006655:Histone Deacetylases / Q000235:genetics*; D006801:Humans; D051379:Mice; D008957:Models, Genetic; D009154:Mutation
chemical_list: C499033:Hdac6 protein, mouse; D000073864:Histone Deacetylase 6; D006655:Histone Deacetylases