The physiological role of the dystrophin protein and pathological conditions in its deficiency

Dystrophin is a crucial structural rod-shaped protein that stabilizes muscle cell membranes and ensures the normal functioning of skeletal musculature. It is an integral component of the dystrophin-associated glycoprotein complex, which serves as a molecular link connecting the myocyte cytoskeleton to the extracellular matrix. Mutations in the DMD gene, located on the short arm of the X chromosome (Xp21.2), result in the complete or partial loss of dystrophin expression. This deficiency compromises sarcolemmal integrity, leading to uncontrolled calcium influx into the cell, subsequent myocyte destruction, oxidative stress, and chronic inflammation. These pathological cascades are accompanied by progressive necrosis of muscle fibers and their gradual replacement by connective and adipose tissue. The most severe clinical manifestation of dystrophin deficiency is Duchenne muscular dystrophy, an X-linked hereditary neuromuscular disorder with an incidence of approximately one in 3500 to 5000 live male births. The disease is characterized by relentless progression, culminating in the loss of ambulation, respiratory insufficiency, and the development of cardiomyopathy. Current scientific perspectives on dystrophin function extend significantly beyond the mechanical stabilization of muscle tissue. Recent studies indicate that this protein plays a critical role in systemic lipid metabolism and central nervous system activity, thereby elucidating the presence of cognitive disorders and metabolic disturbances in patients. This review provides comprehensive information on the structural organization of dystrophin isoforms, the molecular architecture of the dystrophin-associated protein complex, and a detailed analysis of the pathophysiological processes associated with dystrophin deficiency.