Growth differentiation factor 8 (Myostatin) (MSTN)

Growth differentiation factor 8 (Myostatin) is a secreted member of the TGF-beta superfamily that serves as a critical negative regulator of skeletal muscle growth (UniProt P54762). It is synthesized as a precursor protein known as pro-myostatin, which consists of an N-terminal pro-domain and a C-terminal mature domain; this proform is sequestered in the extracellular matrix in a latent state (PubMed: 29346549). To become biologically active, the pro-myostatin must undergo a two-step proteolytic cleavage process: first by furin-like proteases to create a latent complex, and second by BMP-1/tolloid-like metalloproteinases to release the active signaling dimer (PubMed: 30531905). Therapeutic strategies targeting the myostatin proforms, such as the monoclonal antibody apitegromab, aim to prevent this activation process locally within the muscle, thereby promoting muscle hypertrophy and increasing strength (Scholar Rock, 2023). This approach is currently being investigated for the treatment of neuromuscular disorders like spinal muscular atrophy (SMA) and age-related sarcopenia, offering a more specific mechanism than targeting the mature protein or its ubiquitous receptors.

Other names

GDF8GDF-8Pro-myostatinLatent myostatinMyostatin pro-complex

Inhibition of the proteolytic activation of the myostatin precursor (pro-myostatin) or the latent complex, preventing the release of the active mature growth factor and subsequent signaling through the ActRIIB receptor.