Role of caspases in neuronal apoptosis

Caspases play a key role in the integration of specific cellular signaling events that ultimately result in apoptosis or “programmed cell death.” Apoptosis plays an important role during development and in normal cellular homeostasis. However, the inappropriate triggering of apoptotic pathways can have severe consequences that may contribute either directly or indirectly to a number of pathologies. Recognition of the key role of caspases in the apoptotic process has led a number of pharmaceutical and biotechnology companies to pursue the development of specific caspase inhibitors as therapeutic agents. However, no drug targeting this mechanism has yet been marketed. In this review we reflect on the role of caspases in a number of neuronal disorders and neurodegenerative diseases. We also review recent progress in the generation of caspase inhibitors and the challenges faced in their development as therapeutic agents for neurological indications. Drug Dev. Res. 52:515–533, 2001. © 2001 Wiley-Liss, Inc.