Congenital myopathies: pathophysiological mechanisms and promising therapies

Figures

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  Fig. 1. Schematic diagram of the structure of the triad. The sarcoplasmic reticulum is a specialized smooth endoplasmic reticulum in the myofibrils, which is enlarged at both ends to form a flat sac known as the terminal cisterna. The sarcolemma, located at the site of the terminal cisterna, forms funnel-like invaginations, called T-tubules. The T-tubules in skeletal muscle cells are connected to the sarcoplasmic reticulum on both sides, forming a tightly adherent membrane contact called the “triad”

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  Fig. 2. Schematic diagram of fine myofilament composition and actin-myosin interactions. Troponin and tropomyosin act as protein switches that regulate actin-myosin interactions in response to changes in Ca2+ concentration within the myocyte. (a and b) When nerve impulses reach myofibers, Ca2+ is released from the sarcoplasmic reticulum and interacts with troponin complexes, Nebulin, and tropomyosin, leading to conformational changes in the thin filaments to expose myosin binding sites. (c and d) ATP is decomposed into ADP and inorganic phosphate, thereby releasing energy. The energy is utilized by the myosin head, causing the myosin head to bend and move forward. Myosin with the altered conformation binds to actin to form a muscle bridge. The forward movement of the myosin head shortens the distance between actin and myosin, resulting in actin slipping away from myosin and binding to new myosin to form a new muscle bridge. The above steps are repeated. The constant interaction between actin and myosin leads to muscle contraction, thereby generating force. Mutations in genes such as NEB, ACTA1, TNNT1, TPM2, and TPM3, which encode key proteins involved in the above process, result in…