NeuroHeal Reduces Muscle Atrophy and Modulates Associated Autophagy

Cells. 2020 Jun 28;9(7):1575. doi: 10.3390/cells9071575.

Abstract

Muscle wasting is an unmet medical need which leads to a reduction of myofiber diameter and a negative impact on the functional performance of daily activities. We previously found that a new neuroprotective drug called NeuroHeal reduced muscle atrophy produced by transient denervation. Aiming to decipher whether NeuroHeal has a direct role in muscle biology, we used herein different models of muscle atrophy: one caused by chronic denervation, another caused by hindlimb immobilization, and lastly, an in vitro model of myotube atrophy with Tumor Necrosis Factor-α (TNFα). In all these models, we observed that NeuroHeal reduced muscle atrophy and that SIRT1 activation seems to be required for that. The treatment downregulated some critical markers of protein degradation: Muscle Ring Finger 1 (MuRF1), K48 poly-Ub chains, and p62/SQSTM1. Moreover, it seems to restore the autophagy flux associated with denervation. Hence, we envisage a prospective use of NeuroHeal at clinics for different myopathies.

Keywords: NeuroHeal; autophagy; proteasome; sirtuin 1; skeletal muscle atrophy.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acamprosate / therapeutic use*
  • Animals
  • Autophagy / drug effects
  • Cell Line
  • Drug Combinations
  • Immunoblotting
  • Mice
  • Mice, Inbred C57BL
  • Muscle, Skeletal / drug effects
  • Muscle, Skeletal / metabolism
  • Muscular Atrophy / drug therapy*
  • Muscular Atrophy / metabolism
  • Prospective Studies
  • Proteasome Endopeptidase Complex / drug effects
  • Proteasome Endopeptidase Complex / metabolism
  • Ribavirin / therapeutic use*
  • Sirtuin 1 / metabolism

Substances

  • Drug Combinations
  • acamprosate, ribavirin drug combination
  • Ribavirin
  • Proteasome Endopeptidase Complex
  • Sirtuin 1
  • Acamprosate