Oxidative stress-induced death in the nervous system: cell cycle dependent or independent?

Neuronal death, attributable to perturbed redox homeostasis, is the underlying factor in many acute and chronic neurological disorders. The mechanisms employed by oxidatively stressed neurons to commit to cell death pathways are beginning to be characterized, but this is hampered by a lack of good models that extrapolate readily to redox-dependent neuronal death paradigms. In this Mini-Review, we discuss mechanisms by which oxidative stress can result in neurodegeneration. We examine evidence on which terminally differentiated neurons might commit to death under conditions of oxidative stress. In some cases, death may be linked to an aberrant and uncoordinated reentry into the cell cycle and mitotic catastrophe. Other evidence suggests that cell cycle reentry is not mandatory for death execution. Rather, the reexpression of cell cycle proteins may induce apoptotic pathways in a cell cycle-independent manner. In contrast to these models, there is also evidence that oxidative neuronal death is independent of cell cycle proteins. We conclude that oxidative stress-induced neuronal death may be promoted via several pathways, which may be cycle protein dependent or independent. The determining factor for which or how many pathways are induced appears to be context dependent and determined by the level and duration of oxidative stress.