HDAC4-myogenin axis as an important marker of HD-related skeletal muscle atrophy

PLoS Genetics
Michal MielcarekG P Bates

Abstract

Skeletal muscle remodelling and contractile dysfunction occur through both acute and chronic disease processes. These include the accumulation of insoluble aggregates of misfolded amyloid proteins that is a pathological feature of Huntington's disease (HD). While HD has been described primarily as a neurological disease, HD patients' exhibit pronounced skeletal muscle atrophy. Given that huntingtin is a ubiquitously expressed protein, skeletal muscle fibres may be at risk of a cell autonomous HD-related dysfunction. However the mechanism leading to skeletal muscle abnormalities in the clinical and pre-clinical HD settings remains unknown. To unravel this mechanism, we employed the R6/2 transgenic and HdhQ150 knock-in mouse models of HD. We found that symptomatic animals developed a progressive impairment of the contractile characteristics of the hind limb muscles tibialis anterior (TA) and extensor digitorum longus (EDL), accompanied by a significant loss of motor units in the EDL. In symptomatic animals, these pronounced functional changes were accompanied by an aberrant deregulation of contractile protein transcripts and their up-stream transcriptional regulators. In addition, HD mouse models develop a significant reduction i...Continue Reading

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Citations

Jan 23, 2016·Epigenomics·Eros Di Giorgio, Claudio Brancolini
Oct 16, 2015·Rare Diseases·Michal Mielcarek
Dec 17, 2015·Clinical and Translational Medicine·Michal Mielcarek, Mark Isalan
Sep 22, 2015·Cell Reports·Shanshan HuangXiao-Jiang Li
Apr 30, 2016·Pharmacological Reports : PR·Elżbieta CzarnowskaStefan Chłopicki
Dec 3, 2016·Nucleosides, Nucleotides & Nucleic Acids·Marta ToczekRyszard T Smolenski
Dec 3, 2016·Journal of the American College of Cardiology·Brian C Jensen, Monte S Willis
Dec 28, 2018·Nucleosides, Nucleotides & Nucleic Acids·Marta ToczekRyszard T Smolenski
Sep 12, 2018·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Yann S GallotAshok Kumar
Jan 10, 2019·EMBO Reports·Keisuke HitachiKunihiro Tsuchida
Oct 29, 2017·Scientific Reports·Marie K BondulichGillian P Bates
Nov 20, 2019·Journal of Cachexia, Sarcopenia and Muscle·Ligia M Antunes-CorreaCarlos Eduardo Negrão
May 21, 2020·American Journal of Physiology. Cell Physiology·Daniel R MirandaAndrew A Voss
Sep 17, 2020·Nucleosides, Nucleotides & Nucleic Acids·Marta TomczykRyszard T Smolenski
Dec 3, 2016·The Journal of General Physiology·Daniel R MirandaAndrew A Voss
Mar 1, 2019·Journal of Huntington's Disease·Kerstin KojerMichael Orth
Jul 11, 2020·International Journal of Molecular Sciences·Ekaterina P MochalovaTatiana L Nemirovskaya
Apr 20, 2020·Acta Neuropathologica·Samir R NathAndrew P Lieberman
Jul 10, 2019·Journal of Neuroscience Research·Nicholas R FranichMarie-Francoise Chesselet
Jun 8, 2018·Frontiers in Physiology·Bethan J CritchleyMichal Mielcarek
Nov 11, 2020·International Journal of Molecular Sciences·Manuela Bozzi, Francesca Sciandra
Dec 4, 2020·Neural Regeneration Research·Michal Mielcarek, Mark Isalan
Jul 3, 2021·International Journal of Molecular Sciences·Marta TomczykRyszard T Smolenski
Oct 14, 2021·PloS One·Michal Mielcarek, Mark Isalan

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Methods Mentioned

BETA
biopsy
transgenic
ELISA
SMA
PCR

Software Mentioned

geNorm
Picoscope
Excel
Pico
PerfectProbe

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