Implication of cysteine proteases calpain, cathepsin and caspase in ischemic neuronal death of primates

Although more than 8000 papers of apoptosis are published annually, there a re very few reports concerning necrosis in the past few years. A number of recent studies using lower species animals have suggested that the cornu Am monis (CA) 1 neuronal death after brief global cerebral ischemia occurs by apoptosis, an active and genetically controlled cell suicide process. Howev er, the studies of monkeys and humans rather support necrosis, the calpain- mediated release of lysosomal enzyme cathepsin after ischemia conceivably c ontributes to the cell degeneration of CAI neurons. This paper provides an overview of recent developments in ischemic neuronal death, presents the ca scade of the primate neuronal death with particular attentions to the cyste ine proteases, and also indicates selective cathepsin inhibitors as a never neuroprotectant. Furthermore, the possible interaction of calpain, catheps in, and caspase in the cascade of ischemic neuronal death is discussed. (C) 2000 Elsevier Science Ltd. All rights reserved.