HDAC4-Myogenin Axis As an Important Marker of HD-Related Skeletal Muscle Atrophy

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Huntington’s disease (HD) is a neurodegenerative disorder in which the mutation results in an extra-long tract of glutamines that causes the huntingtin protein to aggregate. It is characterized by neurological symptoms and brain pathology, which is associated with nuclear and cytoplasmic protein aggregates and with transcriptional deregulation. Despite the fact that HD has been recognized principally as a neurological disease, there are multiple studies indicating that peripheral pathologies including cardiac dysfunction and skeletal muscle atrophy, contribute to the overall progression of HD. To unravel the cause of the skeletal muscle dysfunction, we applied a wide range of molecular and physiological methods to the analysis of two well established genetic mouse models of this disease. We found that symptomatic animals developed muscle dysfunction characterised by a change in the contractile characteristics of fast twitch muscles and a decrease in twitch and tetanic force of hindlimb muscles. In addition, there is a significant decrease in the number of motor units innervating the EDL muscle, and this motor unit loss progresses during the course of the disease. These changes were accompanied by the re-expression of contractile transcripts and markers of muscle denervation such as the HDAC4-Dach2-myogenin axis, as well as the apparent deterioration in energy metabolism and decreased oxidation. Therefore, we conclude, that the HD-related skeletal muscle atrophy is accompanied by progressive loss of functional motor units.

Vyšlo v časopise: HDAC4-Myogenin Axis As an Important Marker of HD-Related Skeletal Muscle Atrophy. PLoS Genet 11(3): e32767. doi:10.1371/journal.pgen.1005021
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.pgen.1005021

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