The biochemistry of neuronal necrosis: Rogue biology?

When stressed beyond their tolerance, cells undergo necrosis, an acute, non-apoptotic form of cell death. Necrosis is crucial to the damage that injury and disease inflict on the nervous system. Recent discoveries have shed light onto the molecular requirements for necrosis, and provide new evidence that, as is the case for apoptosis, the mechanisms of necrotic cell death are conserved from nematodes to humans. But in contrast to apoptotic mechanisms, necrotic mechanisms did not evolve specifically to carry out necrosis. Instead, under extreme circumstances, normal cellular activities are destabilized with devastating consequences for the cell. Here, we review the mechanisms that are implicated in necrosis and discuss the events that transform them to catastrophic for cell survival.