title: Calpains and human disease.
abstract: Calpains, particularly conventional dimeric calpains, have claimed to be involved in the cell degeneration processes that characterize numerous disease conditions linked to dysfunctions of cellular Ca2+ homeostasis. The evidence supporting their involvement has traditionally been indirect and circumstantial, but recent work has added more solid evidence supporting the role of ubiquitous dimeric calpains in the process of neurodegeneration. The only disease condition in which a calpain defect has been conclusively involved concerns an atypical monomeric calpain: the muscle specific calpain-3, also known as p94. Inactivating defects in its gene cause a muscular dystrophy termed LGMD-2A. The molecular mechanism by which the absence of the proteolytic activity of calpain-3 causes the dystrophic process is unknown. Another atypical calpain, which has been characterized recently as a Ca2(+)-dependent protease, calpain 10, appears To be involved in the etiology of type 2 diabetes. The involvement has been inferred essentially from genetic evidence. Also in the case of type 2 diabetes the molecular mechanisms that could link the disease to calpain 10 are unknown.
authors.affiliation: Department of Biochemistry, University of Padova, Italy.
authors.forename: I
authors.initials: I
authors.lastname: Bertipaglia
authors.forename: E
authors.initials: E
authors.lastname: Carafoli
mesh_terms: D000818:Animals; D002118:Calcium / Q000502:physiology; D002135:Calcium-Binding Proteins / Q000502:physiology; D002154:Calpain / Q000737:chemistry / Q000235:genetics / Q000502:physiology; D064211:Connectin; D003924:Diabetes Mellitus, Type 2 / Q000503:physiopathology*; D006801:Humans; D009124:Muscle Proteins / Q000502:physiology; D049288:Muscular Dystrophies, Limb-Girdle / Q000503:physiopathology*; D019636:Neurodegenerative Diseases / Q000503:physiopathology*; D011494:Protein Kinases / Q000502:physiology
chemical_list: D002135:Calcium-Binding Proteins; D064211:Connectin; D009124:Muscle Proteins; C577285:TTN protein, human; C033668:calpastatin; D011494:Protein Kinases; C105884:CAPN3 protein, human; D002154:Calpain; D002118:Calcium