ABSTRACT
Calpains refer to a family of intracellular non-lysosomal cysteine proteases. They are regulatory rather than digestive proteases because of limited substrate proteolysis. Activation of calpains at neutral pH distinguishes them from other cysteine proteases such as cathepsins. Most calpains have widespread distribution in various tissues of the body. The bestcharacterized isoforms µ-calpain and m-calpain are the predominant calpains in the central nervous system (CNS). At least in vitro, µ-calpain and m-calpain (a.k.a. calpain-1 and calpain-2) are activated by µM and nearly mM Ca2+ concentrations, respectively. Considering their numerous important functions in the CNS, identifying plausible biomarkers for calpain activation represents a major advancement for the diagnosis and treatment of brain diseases and for better understanding of their individual physiological roles. This is a challenging and complicated task as µ-calpain and m-calpain have overlapping substrate specifi city and because the presence of substrate degradation products cannot distinguish between activation of these two calpains.
