Cellular and molecular themes in apoptosis

Apoptosis, an active mechanism of cell death, is of central importance in many biological scenarios. Research in this area has the potential to contribute to our understanding of many diseases and raises several potential therapeutic opportunities. Given this potential and the speed with which our understanding of this field has advanced over recent years, it is timely to introduce the clinician to the background on which the clinical implications of this research will be built. This review begins with contrasting apoptosis with the other mechanism of cell death, necrosis, and then outlines the features by which apoptosis may be recognised. With a view to understanding the level at which this process may be involved in disease and therapeutics, it is important to be aware of the basic mechanistic features of the induction and execution of apoptosis. In this, surface molecules such as CD95 (Fas) and the cascade of intracellular enzymes involved at many levels in apoptosis, the caspases, are of central importance. In all this, the mitochondrion is crucial to the induction of apoptosis and the regulation of the whole process. In the last part of this review, we attempt to draw out the clinical relevance of all this information. It is clear that apoptosis has an important role in the pathophysiology of malignancy, particularly with respect to haematological cancers, but also other oncological diseases. Apoptosis is also very important in autoimmune disease and viral infection. Finally, it is clear that apoptosis may be manipulated therapeutically to the benefit of patients in various scenarios. This is clearly an exciting area for future development, but one which clearly depends on a thorough mechanistic understanding.