Caspases: potential targets for regulating cell death.
While in multicellular organisms all cells inexorably die, there are several different ways provided for the realization of cell death. One of them, apoptosis, represents a universal energy-dependent and tightly regulated physiologic process of cell death in both normal and pathologic tissues. The execution of apoptosis appears to be uniformly mediated through consecutive activation of the members of a caspase family. This review briefly summarizes current knowledge on the molecular mechanisms of caspase activation and the inhibitory components of caspase cascades. The suitability of caspases as a new potential therapeutic target is discussed next. Particular attention is focused on two broad categories of caspase-directed compounds: highly specific caspase inhibitors that distinctly block the progress of apoptosis and caspase activators that selectively induce cell death in a variety of in vitro and in vivo systems. These agents promise to be useful clinically, either alone or in combination with more conventional therapeutics.
Philchenkov
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Mechanisms of Leukemogenesis Laboratory, R.E. Kavetsky Institute of Experimental Pathology, Oncology, and Radiobiology, Vasilkovskaya Str. 45, 03022 Kiev, Ukraine. apoclub@mail.ru
D000818:Animals; D017209:Apoptosis; D061945:Caspase Inhibitors; D020169:Caspases / Q000378:metabolism*; D045304:Cytochromes c / Q000378:metabolism; D004789:Enzyme Activation; D004791:Enzyme Inhibitors / Q000737:chemistry / Q000494:pharmacology*; D015971:Gene Expression Regulation, Enzymologic; D006801:Humans; D008928:Mitochondria / Q000378:metabolism; D008954:Models, Biological; D008956:Models, Chemical; D009369:Neoplasms / Q000188:drug therapy; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism
D061945:Caspase Inhibitors; D004791:Enzyme Inhibitors; D019253:Proto-Oncogene Proteins c-bcl-2; D045304:Cytochromes c; D020169:Caspases