title: The sarcomeric cytoskeleton as a target for pharmacological intervention.
abstract: Many diseases of heart and skeletal muscle, from heart failure to muscle atrophy, pose unmet needs for specific and effective treatments. Recent advances suggest that sarcomeres, the smallest contractile units of heart and skeletal muscles, can be viable pharmacological targets. In sarcomeres, the contractile actin and myosin filaments are organised by a network of proteins combining structural and signalling functions, forming the sarcomeric cytoskeleton. This includes the giant proteins titin, obscurin and nebulin, which contain protein-binding sites along with signalling domains such as protein kinase, Rho activator, and Src-homology domains. These signalling domains have recently been implicated in sarcomere assembly, and the regulation of muscle contractile and metabolic adaptation. Although many functions of sarcomeric proteins remain to be discovered, their potential as pharmacological targets is now emerging. Here, we will review recent insight into the physiological and pathological signalling functions of sarcomeric cytoskeletal proteins and discuss new aspects and strategies in skeletal muscle signalling, pathomechanisms and therapy.
authors.affiliation: King's College London BHF Centre of Research Excellence, Randall Division for Cell and Molecular Biophysics and Cardiovascular Division, New Hunt's House, Guy's Campus, London SE1 1UL, United Kingdom.
authors.forename: Ay Lin
authors.initials: AL
authors.lastname: Kho
authors.forename: Sue
authors.initials: S
authors.lastname: Perera
authors.forename: Alexander
authors.initials: A
authors.lastname: Alexandrovich
authors.forename: Mathias
authors.initials: M
authors.lastname: Gautel
mesh_terms: D008841:Actin Cytoskeleton / Q000187:drug effects*; D000818:Animals; D056966:Excitation Contraction Coupling / Q000187:drug effects; D006331:Heart Diseases / Q000188:drug therapy* / Q000378:metabolism; D006801:Humans; D058990:Molecular Targeted Therapy; D009124:Muscle Proteins / Q000037:antagonists & inhibitors* / Q000737:chemistry / Q000378:metabolism; D009135:Muscular Diseases / Q000188:drug therapy* / Q000378:metabolism; D012518:Sarcomeres / Q000187:drug effects*
chemical_list: D009124:Muscle Proteins