Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0086543 (cataract)
 29,165 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Increasing evidence now suggests that excessive activation of the Ca(2+)-dependent protease calpain could play a key or contributory role in the pathology of a variety of disorders, including cerebral ischaemia, cataract, myocardial ischaemia, muscular dystrophy and platelet aggregation. In this review, Kevin Wang and Po-Wai Yuen discuss the evidence linking these disorders to calpain overactivation. At present, it is difficult to confirm the exact role of calpain in these disorders because of the lack of potent, selective and cell-permeable calpain inhibitors. However, given the multiple therapeutic indications for calpain, it appears that achievement of selective calpain inhibition is an important pharmacological goal.
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PMID:Calpain inhibition: an overview of its therapeutic potential. 785 6

The calpains form a growing family of structurally related intracellular multidomain cysteine proteinases containing a papain-related catalytic domain, whose activity depends on calcium. The calpains are believed to play important roles in cytoskeletal remodeling processes, cell differentiation, apoptosis and signal transduction, but are also implicated in muscular dystrophy, cardiac and cerebral ischemia, platelet aggregation, restenosis, neurodegenerative diseases, rheumatoid arthritis and cataract formation. The best characterized calpains, the ubiquitously expressed mu- and m-calpains, are heterodimers consisting of a common 30-kDa small and a variable 80-kDa subunit. The recently determined crystal structures of human and rat m-calpain crystallized in the absence of calcium essentially explain the inactivity of the apoform by catalytic domain disruption, indicate several sites where calcium could bind causing reformation of a papain-like catalytic domain, and additionally reveal modes by which phospholipid membranes could reduce the calcium requirement. Current evidence points to a cooperative interaction of several sites, which, upon calcium binding, trigger the reformation of a papain-similar catalytic domain.
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PMID:The structure of calcium-free human m-calpain: implications for calcium activation and function. 1167 52