Necrosis, Apoptosis, and Autophagy: Mechanisms of Neuronal and Glial Cell Death

Most neurodegenerative diseases culminate in cell death, although it is not uncommon for signs of dysfunction to precede cell death in humans and animal models. There is considerable evidence that neuronal and glial cell death during development occurs through apoptosis but whether apoptosis occurs during degeneration is still a contentious issue. Apoptosis is a well-defined process with key steps that mark the progress of the process in individual cells. Necrosis and autophagy as primary causes of death are less well defined. Two issues need particular clarification: (1) when is necrosis deemed to be the death mechanism rather than a secondary outcome of another death mechanism, and (2) whether the autophagic process, or its deficiency, causes death, or whether autophagy is a bystander (or survival) effect. Here we present a framework for addressing how to discern when necrosis, apoptosis, and/or autophagy occur in primary cultures of neurons and glia.