Caspase-independent cell death

Abstract

Caspase-mediated apoptosis is the death program of choice in many developmental and physiologic settings. It would, however, be very dangerous for the organism to depend on a single protease family for clearance of unwanted and potentially dangerous cells. Indeed, the exclusive role of caspases in the execution of programmed cell death (PCD) has been challenged recently. Since the first reports on caspaseindependent PCD in the late 1990s, over 200 papers have been published on the topic. Now our understanding of the molecular control of alternative death pathways is growing, like that of the molecular anatomy of apoptosis at the time of the discovery of caspases less than a decade ago. Here, we review recently discovered triggers and molecular regulators of alternative cell-death programs and discuss the implications of the death mode for the surrounding tissue and the potential of caspase- independent PCD signaling pathways as therapeutic targets for the treatment of cancer and neurodegenerative disorders.