Troponin C, fast skeletal muscle (TNNC2) (TNNC2)

Troponin C, fast skeletal muscle (TNNC2) is a calcium-binding protein that serves as a critical regulatory subunit of the troponin complex in fast-twitch skeletal muscle fibers (UniProt P02585). It acts as a molecular switch, where the binding of calcium ions to its N-terminal regulatory sites induces a conformational change that allows the interaction between actin and myosin, thereby initiating muscle contraction (Wikipedia, TNNC2). TNNC2 is a key therapeutic target for neuromuscular diseases characterized by muscle weakness and fatigue, such as amyotrophic lateral sclerosis (ALS), spinal muscular atrophy (SMA), and myasthenia gravis (NIH, PMC3296825). Pharmacological activation of TNNC2 using small molecules known as fast skeletal muscle troponin activators (FSTAs), such as tirasemtiv and reldesemtiv, sensitizes the muscle to calcium and increases force production at submaximal levels of nerve stimulation (J Med Chem, 2021). Mutations in the TNNC2 gene have also been linked to congenital myopathies, highlighting its essential role in maintaining normal muscle function (J Clin Invest, 2021). Therapeutic development in this area focuses on improving muscle strength and respiratory function while minimizing central nervous system side effects like dizziness (ALS.net, 2019).

Other names

Troponin C2, fast skeletal typefsTnCsTnCCFAP85FAP85

Fast skeletal muscle troponin activator (FSTA) that sensitizes the sarcomere to calcium by slowing the rate of calcium release from the troponin complex, thereby increasing muscle force production at submaximal nerve stimulation frequencies (NIH, PMC3296825; J Med Chem, 2021).