Ca 2+ signals and death programmes in neurons

Abstract

Cell death programmes are generally defined by biochemical/genetic routines that are linked to their execution and by the appearance of more or less typical morphological features. However, in pathological settings death signals may engage complex and interacting lethal pathways, some of which are common to different cells, whereas others are linked to a specific tissue and differentiation pattern. In neurons, death programmes can be spatially and temporally segregated. Most importantly physiological Ca 2+ signals are essential for cell function and survival. On the other hand, Ca 2+ overload or perturbations of intracellular Ca 2+ compartmentalization can activate or enhance mechanisms leading to cell death. An imbalance between Ca 2+ influx and efflux from cells is the initial signal leading to Ca 2+ overload and death of ischaemic neurons or cardiomyocytes. Alterations of intracellular Ca 2+ storage can integrate with death signals that do not initially require Ca 2+ , to promote processing of cellular components and death by apoptosis or necrosis. Finally, Ca 2+ can directly activate catabolic enzymes such as proteases, phospholipases and nucleases that directly cause cell demise and tissue damage.