Neuronal cell death in the mammalian nervous system: the calmortin hypothesis.

1. This review is concerned with the calcium-dependent mechanisms involved in neuronal cell death. To this end, it provides definitions of the major types of cell death and then describes what is known of their occurrence during development and degeneration of the mammalian nervous system. 2. An analysis is presented of the different sources and compartments of calcium in neurons and of how these are related to the known calcium-dependent enzymes whose excess activation will lead to cell death. 3. The review uses the relatively large amount of pertinent information now available for other cell types, especially thymocytes, to reveal our limited knowledge of how calcium controls neuronal cell death. 4. In the final section, consideration is given to the identification of those factors that may mitigate against the calcium-dependent pathways leading to neuronal degeneration.