From birth to death: A role for reactive oxygen species in neuronal development.

Historically, ROS have been considered toxic molecules, especially when their intracellular concentration reaches high values. However, physiological levels of ROS support crucial cellular processes, acting as second messengers able to regulate intrinsic signaling pathways. Specifically, both the central and peripheral nervous systems are especially susceptible to changes in the redox state, developing either a defense or adaptive response depending on the concentration, source and duration of the pro-oxidative stimuli. In this review, we summarize classical and modern concepts regarding ROS physiology, with an emphasis on the role of the NADPH oxidase (NOX) complex, the main enzymatic and regulated source of ROS in the nervous system. We discuss how ROS and redox state contribute to neurogenesis, polarization and maturation of neurons, providing a context for the spatio-temporal conditions in which ROS modulate neural fate, discriminating between "oxidative distress", and "oxidative eustress". Finally, we present a brief discussion about the "physiological range of ROS concentration", and suggest that these values depend on several parameters, including cell type, developmental stage, and the source and type of pro-oxidative molecule.