Calpain and caspase: can you tell the difference?

Both necrotic and apoptotic neuronal death ave observed in various neurological and neurodegenerative disorders. Calpain is activated in various necrotic and apoptotic conditions, while caspase 3 is only activated in neuronal apoptosis, Despite the difference in cleavage-site specificity, an increasing number of cellular proteins are found to be dually susceptible to these cysteine proteases, These include alpha- and beta-fodrin, calmodulin-dependent protein kinases, ADP-ribosyltransferase (ADPRT/PARP) and tau, Intriguingly, calpastatin is susceptible to caspase-mediated fragmentation. Neurotoxic challenges such as hypoxia-hypoglycemia, excitotoxin treatment or metabolic inhibition of cultured neurons result in activation of both proteases, Calpain inhibitors can protect against necrotic neuronal death and, to a lesser extent, apoptotic death. Caspase inhibitors strongly suppress apoptotic neuronal death. Thus, both protease families might contribute to structural derangement and functional loss in neurons under degenerative conditions.