Calpain and caspase: can you tell the difference?
Both necrotic and apoptotic neuronal death are 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.
Wang
K K
KK
Dept of Neuroscience Therapeutics, Parke-Davis Pharmaceutical Research, Warner-Lambert Company, Ann Arbor, MI 48105, USA. kevin.wang@wl.com
D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D001927:Brain Diseases / Q000188:drug therapy / Q000378:metabolism*; D002154:Calpain / Q000009:adverse effects / Q000378:metabolism*; D020169:Caspases / Q000009:adverse effects / Q000378:metabolism*; D015853:Cysteine Proteinase Inhibitors / Q000378:metabolism; D006801:Humans; D009336:Necrosis; D018696:Neuroprotective Agents / Q000378:metabolism
D015853:Cysteine Proteinase Inhibitors; D018696:Neuroprotective Agents; D002154:Calpain; D020169:Caspases