Growth differentiation factor 8 (MSTN) (MSTN)

Myostatin, encoded by the MSTN gene, is a secreted growth factor and member of the transforming growth factor-beta (TGF-beta) superfamily that acts as a potent negative regulator of skeletal muscle mass (UniProt, 1.2.1; NIH, 1.1.1). It is primarily synthesized in skeletal muscle as an inactive precursor (promyostatin) and undergoes proteolytic cleavage to release a mature C-terminal dimer that binds to activin type II receptors (ActRIIB), triggering a SMAD2/3 signaling cascade that inhibits muscle protein synthesis and myoblast differentiation (Wikipedia, 1.2.2; PatSnap, 1.3.2). Genetic loss-of-function mutations in the MSTN gene lead to dramatic muscle hypertrophy, a phenotype observed in several species including humans (NIH, 1.5.1). Due to its role in limiting muscle growth, myostatin is a major therapeutic target for treating muscle-wasting conditions such as sarcopenia, muscular dystrophy, and cancer cachexia, as well as metabolic disorders like obesity and type 2 diabetes (Frontiers, 1.1.1; NIH, 1.3.4). Various pharmacological strategies, including monoclonal antibodies (e.g., apitegromab, domagrozumab) and soluble receptor decoys (e.g., ACE-031), have been developed to neutralize myostatin activity, though clinical development has faced challenges regarding specificity and functional outcomes (NIH, 1.3.1; Wikipedia, 1.3.3).

Other names

MyostatinGDF8GDF-8Growth/differentiation factor 8MSLHP

Inhibition of myostatin signaling by binding to the mature protein, the pro-form, or the latent complex to prevent its interaction with activin type II receptors (ActRIIB/ActRIIA).