TY - JOUR
T1 - Charcot-Marie-Tooth disease
T2 - Emerging mechanisms and therapies
AU - D'Ydewalle, Constantin
AU - Benoy, Veronick
AU - Van Den Bosch, Ludo
N1 - Funding Information:
Research of the authors is supported by grants from the Fund for Scientific Research Flanders (FWO) , the University of Leuven, the Belgian government (Interuniversity Attraction Poles, program P6/43 of the Belgian Federal Science Policy Office), the Association Belge contre les Maladies neuro-Musculaires (ABMM), the Association Française contre les Myopathies (AFM), the Frick Foundation for Amyotrophic Lateral Sclerosis Research , the Muscular Dystrophy Association (MDA), the European Community's Health Seventh Framework Program (FP7/2007-2013 under grant agreement 259867 ) and the Latran Foundation . C.d.Y. and V.B. are supported by the Agency for Innovation by Science and Technology in Flanders (IWT-Vlaanderen) .
PY - 2012/8
Y1 - 2012/8
N2 - 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.
AB - 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.
KW - Axonal transport
KW - Charcot-Marie-Tooth disease (CMT)
KW - Histone deacetylase 6 (HDAC6)
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U2 - 10.1016/j.biocel.2012.04.020
DO - 10.1016/j.biocel.2012.04.020
M3 - Short survey
C2 - 22575637
AN - SCOPUS:84861476097
SN - 1357-2725
VL - 44
SP - 1299
EP - 1304
JO - International Journal of Biochemistry and Cell Biology
JF - International Journal of Biochemistry and Cell Biology
IS - 8
ER -