Recent progress in elucidating signalling proteolytic pathways in muscle wasting: potential clinical implications

Nutr Metab Cardiovasc Dis. 2013 Dec:23 Suppl 1:S1-5. doi: 10.1016/j.numecd.2012.08.008. Epub 2012 Nov 10.

Abstract

Aims: Muscle wasting prevails with disuse (bedrest and immobilisation) and is associated with many diseases (cancer, sepsis, diabetes, kidney failure, trauma, etc.). This results first in prolonged hospitalisation with associated high health-care costs and second and ultimately in increased morbidity and mortality. The precise characterisation of the signalling pathways leading to muscle atrophy is therefore particularly relevant in clinical settings.

Data synthesis: Recent major papers have identified highly complex intricate pathways of signalling molecules, which induce the transcription of the muscle-specific ubiquitin protein ligases MAFbx/Atrogin-1 and MuRF1 that are overexpressed in nearly all muscle wasting diseases. These signalling pathways have been targeted with success in animal models of muscle wasting. In particular, these findings have revealed a finely tuned crosstalk between both anabolic and catabolic processes.

Conclusions: Whether or not such strategies may be useful for blocking or at least limiting muscle wasting in weight losing and cachectic patients is becoming nowadays a very exciting clinical challenge.

Keywords: Autophagy; MAFbx/Atrogin-1; MuRF1; Muscle wasting; Protein turnover; Signalling pathway; Ubiquitin–proteasome system.

Publication types

  • Review

MeSH terms

  • Bed Rest / adverse effects
  • Humans
  • Muscle Proteins / metabolism
  • Muscle, Skeletal / metabolism*
  • Muscle, Skeletal / pathology*
  • Muscular Atrophy / metabolism*
  • Muscular Atrophy / mortality
  • Muscular Atrophy / pathology*
  • Proteasome Endopeptidase Complex / metabolism
  • Signal Transduction / physiology*
  • Ubiquitin / metabolism

Substances

  • Muscle Proteins
  • Ubiquitin
  • Proteasome Endopeptidase Complex