Effects of Class II-Selective Histone Deacetylase Inhibitor on Neuromuscular Function and Disease Progression in SOD1-ALS Mice

Daniela Buonvicino, Roberta Felici, Giuseppe Ranieri, Riccardo Caramelli, Andrea Lapucci, Leonardo Cavone, Mirko Muzzi, Lorena Di Pietro, Camilla Bernardini, Clemens Zwergel, Sergio Valente, Antonello Mai, Alberto Chiarugi

Risultato della ricerca: Contributo in rivistaArticolo in rivista

11 Citazioni (Scopus)


Emerging evidence indicates that transcriptome alterations due to epigenetic deregulation concur to ALS pathogenesis. Accordingly, pan-histone deacetylase (HDAC) inhibitors delay ALS development in mice, but these compounds failed when tested in ALS patients. Possibly, lack of selectivity toward specific classes of HDACs weakens the therapeutic effects of pan-HDAC inhibitors. Here, we tested the effects of the HDAC Class II selective inhibitor MC1568 on disease evolution, motor neuron survival as well as skeletal muscle function in SOD1G93A mice. We report that HDACs did not undergo expression changes during disease evolution in isolated motor neurons of adult mice. Conversely, increase in specific Class II HDACs (-4, -5 and -6) occurs in skeletal muscle of mice with severe neuromuscular impairment. Importantly, treatment with MC1568 causes early improvement of motor performances that vanishes at later stages of disease. Notably, motor improvement is not paralleled by reduced motor neuron degeneration but by increased skeletal muscle electrical potentials, reduced activation of mir206/FGFBP1-dependent muscle reinnervation signaling, and increased muscle expression of myogenic genes. (C) 2018 IBRO. Published by Elsevier Ltd. All rights reserved.
Lingua originaleEnglish
pagine (da-a)228-238
Numero di pagine11
Stato di pubblicazionePubblicato - 2018


  • Amyotrophic Lateral Sclerosis
  • Animals
  • Animals, Genetically Modified
  • Cell Survival
  • Cells, Cultured
  • Female
  • HDAC inhibitor
  • Histone Deacetylase Inhibitors
  • Histone Deacetylases
  • Hydroxamic Acids
  • Male
  • Motor Activity
  • Motor Neurons
  • Muscle, Skeletal
  • Neuroprotective Agents
  • Pyrroles
  • Random Allocation
  • SOD1G93A mice
  • Sciatic Nerve
  • Superoxide Dismutase
  • amyotrophic lateral sclerosis
  • motor neurons
  • skeletal muscle


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