Growth differentiation factor 8 (GDF-8) (GDF-8)

Growth differentiation factor 8 (GDF-8), commonly known as myostatin, is a member of the transforming growth factor-beta (TGF-beta) superfamily that acts as a potent negative regulator of skeletal muscle mass [1.1.1, 1.2.1]. It is synthesized as a precursor protein (pro-myostatin) that is cleaved by furin-like proteases into an N-terminal pro-domain and a C-terminal mature domain, which remain non-covalently associated to form the inactive latent GDF-8 complex [1.1.3, 1.2.2]. This latent complex circulates in the blood and resides in the extracellular matrix, requiring further proteolytic cleavage by BMP-1/tolloid-like metalloproteinases to release the active mature growth factor [1.2.1, 1.4.1]. In various muscle-wasting conditions, such as spinal muscular atrophy (SMA) and muscular dystrophies, inhibiting GDF-8 signaling is a key therapeutic strategy to promote muscle growth and improve motor function [1.3.1, 1.3.4]. Modern therapeutic approaches, such as the monoclonal antibody apitegromab, specifically target the latent form of GDF-8 to prevent its activation, offering greater selectivity and reducing the risk of off-target effects on related TGF-beta family members [1.3.1, 1.3.3].

Other names

MyostatinMSTNGDF8Growth/differentiation factor 8Pro-myostatinLatent myostatin

Selective inhibition of the activation of the latent GDF-8 complex into its mature, signaling form by binding to the pro-domain or the latent complex, thereby preventing proteolytic cleavage by BMP-1/tolloid-like metalloproteinases and subsequent binding to the Activin type IIB receptor (ActRIIB) [1.2.1, 1.3.1, 1.3.3].