Inhibition of apoptosis: potential clinical targets

Recent advances in the understanding of the molecular mechanisms of apoptosis have allowed researchers to begin targeting undesired apoptosis, in an attempt to moderate its occurrence. Unscheduled apoptosis appears to transpire in numerous diseases, both acute (e.g., stroke, liver degeneration) and chronic (e.g., osteoarthritis, neurodegeneration). There is a clear unmet medical need for better therapies for such diseases. The most active area of research involves a novel family of cysteine proteases which have been termed the caspases. In a number of isolated cell systems, the caspases have been shown to be involved in molecular pathways leading to apoptosis in response to apoptotic stimuli and evidence is mounting for pivotal roles for members of this novel protease family in degenerative diseases. Inhibition of caspase activity is predicted to be beneficial for degenerative diseases and this review summarises the current status and some of the issues of targeting apoptosis as a disease-modifying therapy.