Caspase inhibitors in prevention of apoptosis.

Apoptosis, a morphological distinct form of programmed cell death, is a crucial process during development, the maintenance of cell homeostasis and the regulation of the immune system. A variety of diseases have been found to correlate with physiological apoptosis including cancer, autoimmune disease, viral infection and degenerative disorders. Although very different signals initiate apoptosis, the phenotype of apoptosis is surprisingly similar even in different cell types suggesting that the final stages of apoptotic death are highly conserved. The execution of the death program is coordinated by a recently identified class of cysteine proteases termed caspases. The finding that caspases are mainly involved in regulation of this conserved part of the death program has boosted the search for caspase inhibitors which might offer a therapeutic approach to treat apoptotic disorders. Synthetic peptide inhibitors have been developed which exhibit some selectivity for the different caspases. In the last years several natural inhibitors have been discovered which either prevent caspase activation or caspase activity. This review will present the recent advances and discuss the potential of caspase inhibitors as future therapeutics.