Exploring the Myostatin Activation Pathway: A Promising Target for Treating Muscle Atrophy.

Myostatin is a myokine found in skeletal muscle that acts as a negative regulator of muscle growth. Elevated levels of this protein are linked to muscle atrophy, making it a promising target for therapies aimed at muscle regeneration, particularly in muscular dystrophies. In this study, we investigate the molecular interactions involved in myostatin activation to develop a model for peptide-based inhibitors. Our simulations align with experimental data, identifying the forearm domain of the myostatin precursor as being essential for maintaining its inactive state. Key residues, such as Ile and Leu, play a primary role in stabilizing this interaction. Based on these findings, we propose a peptide-based drug model identifying essential residues and mutable sites to enhance inhibition. Additionally, we identified a previously unreported target site emerging during the final step of myostatin activation. Targeting this site with small molecules could offer a new strategy for preventing myostatin activity and promoting muscle growth.