Sealing one's fate: control of cell death in neurons

BCL-2 family members and caspases are essential components of the death machinery in neurons, Identification of Apaf-1 as the mammalian homologue of Caenorhabditis elegans ced-4 provided the final proof of the complete conservation of the C. elegans programmed cell death pathway in mammals. When neurons are deprived of trophic factors, a sequence of events is initiated, which includes a reduction in macromolecule synthesis, elevation of c-Jun and cyclin D1, and activation of BAX. The final episode of this sequence is the activation of caspases, which may mark the death commitment point at which neurons cannot be rescued by addition of trophic factors. In addition, recent evidence suggests that the components in the developmental programmed cell death pathway may play a critical role in neurodegenerative disorders.