Calpain and caspase: can you tell the difference?

Trends Neurosci. 2000 Jan;23(1):20-6. doi: 10.1016/s0166-2236(99)01479-4.


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.

Publication types

  • Review

MeSH terms

  • Animals
  • Apoptosis / drug effects*
  • Brain Diseases / drug therapy
  • Brain Diseases / metabolism*
  • Calpain / adverse effects
  • Calpain / metabolism*
  • Caspases / adverse effects
  • Caspases / metabolism*
  • Cysteine Proteinase Inhibitors / metabolism
  • Humans
  • Necrosis
  • Neuroprotective Agents / metabolism


  • Cysteine Proteinase Inhibitors
  • Neuroprotective Agents
  • Calpain
  • Caspases