Calcium, free radicals and excitotoxins in neuronal apoptosis

Apoptosis is an active process of cell destruction, characterized by cell shrinkage, chromatin aggregation with extensive genomic fragmentation, and nuclear pyknosis. In contrast, necrosis is characterized by passive cell swelling, intense mitochondrial damage with rapid energy loss, and generalized disruption of internal homeostasis. This swiftly leads to membrane lysis, release of intracellular constituents that evoke a local inflammatory reaction, edema, and injury to the surrounding tissue. In collaboration, our two research laboratories have been defining excitotoxic signals that lead to apoptosis versus necrosis via, among other pathways, Ca2+ signaling mechanisms; this is the subject of this brief review.