Title: HDAC6 inhibition reverses axonal loss in a mouse model of mutant HSPB1-induced Charcot-Marie-Tooth disease
Other Titles: HDAC6 inhibitie herstelt het axonaal verlies in een muismodel voor mutant HSPB1-geïnduceerde ziekte van Charcot-Marie-Tooth
Authors: van Outryve d'Ydewalle, Constantin; M9924121
Issue Date: 26-Jan-2012
Abstract: Charcot-Marie-Tooth disease (CMT) is the most common inherited disorderof the peripheral nervous system. Mutations in the 27-kDa small heat-shock protein ( HSPB1 ) cause axonal CMT or distal hereditary motor neuropathy (distal HMN). We developed and characterized transgenic mice expressing two different HSPB1 mutations (p.S135F and p.P182L) in neurons only. These mice showed all features of CMT or distal HMN dependent on the mutation. Expression of mutant HSPB1 decreased acetylated tubulin abundance and induced severe axonal transport deficits. An increase of tubulin acetylation induced by pharmacological inhibition of histone deacetylase 6 (HDAC6) corrected the axonal transport defects caused by HSPB1 mutations and rescued the CMT phenotype of symptomatic mutant HSPB1 mice. Our findings demonstrate the pathogenic role of tubulin deacetylation inmutant HSPB1-induced neuropathies and offer perspectives for using HDAC6 inhibitors as a therapeutic strategy for hereditary axonopathies.
Publication status: published
KU Leuven publication type: TH
Appears in Collections:Laboratory for Neurobiology (VIB-KU Leuven Center for Brain & Disease Research)
Research Group Experimental Neurology

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