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Immunology‚ Endocrine & Metabolic Agents in Medicinal Chemistry (Formerly Current Medicinal Chemistry - Immunology‚ Endocrine and Metabolic Agents)

Volume 10 Issue 4
ISSN: 1871-5222
eISSN: 1875-5844

 

   All Titles

  Extracellular Regulation of Myostatin: A Molecular Rheostat for Muscle Mass
  pp.183-194 (12) Author: Se-Jin Lee
 
 
      Abstract

Myostatin (MSTN) is a transforming growth factor-β family member that plays a critical role in regulating skeletal muscle mass. Genetic studies in multiple species have demonstrated that mutations in the Mstn gene lead to dramatic and widespread increases in muscle mass as a result of a combination of increased fiber numbers and increased fiber sizes. MSTN inhibitors have also been shown to cause significant increases in muscle growth when administered to adult mice. As a result, there has been an extensive effort to understand the mechanisms underlying MSTN regulation and activity with the goal of developing the most effective strategies for targeting this signaling pathway for clinical applications. Here, I review the current state of knowledge regarding the regulation of MSTN extracellularly by binding proteins and discuss the implications of these findings both with respect to the fundamental physiological role that MSTN plays in regulating tissue homeostasis and with respect to the development of therapeutic agents to combat muscle loss.

 
  Keywords: Myostatin, transforming growth factor-β, skeletal muscle, tissue growth, latency, propeptide, bone morphogenetic protein-1 (BMP-1), tolloid, follistatin, FLRG, Rheostat, FSTL-3, GASP-1, GASP-2, activin type II receptor, metabolic diseases, cDNA, Chinese hamster ovary, inhibitory proteins, ACVR2B, ALK4, ALK5, CHO cells, C2C12 cells, TGF, pro-MSTN, ligands, C-terminal dimer, HPLC, AAV8 vector, wild type, metalloproteases, BMPs, Drosophila, Xenopus, D76A mutation, TLL-2, isoforms, IC50s, FSD1, FSD2, FSD3, monoclonal antibody, Gdf11
  Affiliation: Department of Molecular Biology and Genetics, Johns Hopkins University School of Medicine, PCTB 803, 725 North Wolfe Street, Baltimore, Maryland 21205, USA.
 
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