Neurons bearing presenilins: weapons for defense or suicide?

Abstract

Apoptotic machinery designed for cell's organized self-destruction involve different systems of proteases which cleave vital proteins and disassemble nuclear and cytoplasmic structures, committing the cell to death. The most studied apoptotic proteolytic system is the caspase family, but calpains and the proteasome could play important roles as well. Alzheimer's disease associated presenilins showed to be a substrate for such proteolytic systems, being processed early in several apoptotic models, and recent data suggest that alternative presenilin fragments could regulate cell survival. Mutations in genes encoding presenilins proved to sensitize neurons to apoptosis by different mechanisms e.g. increased caspase-3 activation, oxyradicals production and calcium signaling dysregulation. Here we review the data involving presenilins in apoptosis and discuss a possible role of presenilins in the regulation of apoptotic biochemical machinery.