Past, present, and future perspective of targeting myostatin and related signaling pathways to counteract muscle atrophy

Willem M.H. Hoogaars*, Richard T. Jaspers

*Corresponding author for this work

Research output: Chapter in Book / Report / Conference proceedingChapterAcademicpeer-review

Abstract

Myostatin was identified more than 20 years ago as a negative regulator of muscle mass in mice and cattle. Since then, a wealth of studies have uncovered the potential involvement of myostatin in muscle atrophy and sparked interest in myostatin as a promising therapeutic target to counteract decline of muscle mass in patients afflicted with different muscle-wasting conditions. Insight in the molecular mechanism of myostatin signaling and regulation of myostatin activity has resulted in the identification of specific treatments to inhibit myostatin signaling and related signaling pathways. Currently, several treatments that target myostatin and related proteins have been evaluated in preclinical animal models of muscle wasting, and some potential therapies have progressed to clinical trials. However, studies also revealed potential downsides of myostatin targeting in skeletal muscle and other tissues, which raises the question if myostatin is indeed a valuable target to counteract muscle atrophy. In this review we provide an updated overview of the molecular mechanisms of myostatin signaling, the preclinical evidence supporting a role for myostatin and related proteins in muscle atrophy, and the potential issues that arise when targeting myostatin. In addition, we evaluate the current clinical status of different treatments aimed at inhibiting myostatin and discuss future perspectives of targeting myostatin to counteract muscle atrophy.

Original languageEnglish
Title of host publicationMuscle atrophy
PublisherSpringer New York LLC
Pages153-206
Number of pages54
ISBN (Electronic)9789811314353
ISBN (Print)9789811314346
DOIs
Publication statusPublished - 2018

Publication series

NameAdvances in Experimental Medicine and Biology
Volume1088
ISSN (Print)0065-2598
ISSN (Electronic)2214-8019

Keywords

  • Muscle atrophy
  • Myostatin
  • Signaling pathways
  • Therapy

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