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Trends Neurosci. 2000 Jan;23(1):20-6.

Calpain and caspase: can you tell the difference?

Author information

Dept of Neuroscience Therapeutics, Parke-Davis Pharmaceutical Research, Warner-Lambert Company, Ann Arbor, MI 48105, USA.

Erratum in

  • Trends Neurosci 2000 Feb;23(2):59.


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.

[Indexed for MEDLINE]

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