Role of apoptosis in disease

Abstract

Since the initial description of apoptosis, a number of different forms of cell death have been described. In this review we will focus on classic caspase-dependent apoptosis and its variations that contribute to diseases. Over fifty years of research have clarified molecular mechanisms involved in apoptotic signaling as well and shown that alterations of these pathways lead to human diseases. Indeed both reduced and increased apoptosis can result in pathology. More recently these findings have led to the development of therapeutic approaches based on regulation of apoptosis, some of which are in clinical trials or have entered medical practice.

Figure 1. Schematic representation of the main molecular pathways leading to apoptosis

In the extrinsic pathway upon ligand binding to specific receptors the DISC complex is formed and caspase 8 activated. In the intrinsic pathway release of cyt c from the mitochondria result in the formation of the apoptosome and activation of caspase 9. Caspase 8 and 9 then activate downstream caspases such as caspase 3 resulting in cell death. The two pathways are connected through the cleavage of the BH3 only protein BID.