Calpain as proposed target for neuroprotective treatment of brain ischemia.

Increasing evidence now suggests that excessive activation of calcium-dependent neutral proteases, calpains, could play a key or contributory role in the pathology of cerebral ischemia. This assumption has been supported in part by the suppressive or neuroprotective effects of calpain inhibitors on post-ischemic damage. Targeting calcium-activated proteolysis could be therefore an alternative strategy for protecting neurons against post-ischemic injury. The data of this review indicate that unregulated activation of calcium-dependent proteolysis plays a significant role in the brain damage that occurs following an ischemic insult and that selective and permanent calpain inhibitors may provide a powerfully effective therapeutic means of limiting neuronal damage.