Science & Technology, Life Sciences & Biomedicine, Biochemistry & Molecular Biology, Cell Biology, Charcot-Marie-Tooth disease (CMT), Axonal transport, Histone deacetylase 6 (HDAC6), HEREDITARY MOTOR NEUROPATHY, TRANSFER-RNA SYNTHETASE, MOUSE MODEL, INHERITED NEUROPATHIES, AXONAL NEUROPATHIES, SCHWANN-CELLS, MUTANT, MUTATIONS, TRANSPORT, PROTEIN, Animals, Axonal Transport, Axons, Charcot-Marie-Tooth Disease, Genetic Predisposition to Disease, Histone Deacetylase 6, Histone Deacetylases, Humans, Mice, Models, Genetic, Mutation, 0601 Biochemistry and Cell Biology
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.