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Calpain
- Molecular classification
- Enzyme, Cysteine protease
01
Overview
Calpains are a family of intracellular, calcium-dependent, non-lysosomal cysteine proteases. They are ubiquitously expressed in mammals and many other organisms, playing key roles in various cellular processes by mediating limited proteolysis of specific substrates. The calpain system includes the calpain proteases themselves, a small regulatory subunit (CAPNS1/CAPN4), and an endogenous inhibitor called calpastatin. Dysregulation or overactivation has been implicated as an aggravating factor in various diseases including neurodegeneration after trauma/stroke/myocardial infarction due to excessive substrate cleavage following abnormal increases in intracellular Ca²⁺ levels.
- Other names
- Calcium-activated neutral proteaseCANPμ-Calpainm-CalpainCalpain ICalpain II
02
Mechanism of action
Calpain inhibitors (being developed) aim to reduce excessive proteolysis following calcium dysregulation.
03
Biological functions
Cytoskeleton remodelingSignal transductionApoptosisCell cycle control
04
Disease associations
Neurodegenerative diseaseCardiovascular diseaseStrokeIschemiaMyocardial infarction
05
Safety considerations
Potential for off-target effects due to broad substrate specificity.Inhibition of calpain activity may have unintended consequences on normal cellular function.
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