Molecular machinery and signaling events in apoptosis

Apoptosis is a process of major biomedical interest, since its ineffectiven ess or inappropriate activation appears to be involved in the pathogenesis of a broad variety of human diseases (neoplasia, autoimmune disorders, vira l and neurodegenerative diseases, to name a few). On this topic, extensive experimental work has allowed in the past years the clarification of the co mplex biochemical machinery that commits a cell to apoptosis and executes t he death program. As to the signaling mechanisms, it is now evident that ap optosis can be initiated by different stimuli and/or genetic programs that are differentially decoded inside the cell. While the past years have witne ssed a major advancement on this topic, much still needs to be Learned of t he cross-talk between the various signaling pathways involved in decoding t he apoptotic stimuli, as well as the activation of other cel functions. In this review we first describe the properties and activation mechanisms of t he caspases, the effector proteases of apoptosis. in the second part we dis cuss the current evidence for the involvement of calcium, the ubiquitous se cond-messenger decoding a wide variety of physiological stimuli, and highli ght the potential targets of the apoptotic calcium signal. Drug Dev. Res. 5 2:558-570, 2001. (C) 2002 Wiley-Liss, Inc.