Cell cycle regulation of neuronal apoptosis in development and disease

Apoptosis of neurons is indispensable to the normal development of the nervous system and contributes to neuronal loss in neurologic injury and disease. Life and death decisions are imposed upon neurons by extracellular and intracellular stimuli including the lack of trophic support, exposure to neurotoxins, oxidative stress, and DNA damage. These stimuli induce signaling pathways that are integrated at the mitochondrial apoptotic machinery culminating in cell survival or death. Growing evidence suggests that cell cycle proteins are expressed in dying neurons in the developing and adult brain. However, the role and mechanisms by which re-activation of cell cycle pathways in postmitotic neurons propagates an apoptotic signal to the cell death machinery are just beginning to be characterized. Here, we will review the molecular mechanisms of neuronal cell death and survival with a focus on recent findings on cell cycle regulation of neuronal apoptosis in primary cultures of neurons, mouse models of neuronal diseases, and human neurodegenerative diseases.