Calpains and muscular dystrophies

Calpains are a ubiquitous, well-conserved family of calcium-dependent, cyst eine proteases. Their function in muscle has-received increased interest be cause of the discoveries that the activation and concentration of the ubiqu itous calpains increase in the mouse model of Duchenne muscular dystrophy ( DMD), but null mutations of muscle specific calpain causes limb girdle musc ular dystrophy 2A (LGMD2A). These findings indicate that modulation of calp ain activity contributes to muscular dystrophies;by disrupting normal regul atory mechanisms influenced by calpains, rather than through a general, non specific increase in proteolysis. Thus, modulation of calpain activity or e xpression through pharmacological or moleculargenetic approaches may provid e therapies for some muscular dystrophies. (C) 1999 Elsevier Science Ltd. A ll rights reserved.