Reactive Oxygen Species: Angels and Demons in the Life of a Neuron

Abstract

Reactive oxygen species (ROS) have emerged as regulators of key processes supporting neuronal growth, function, and plasticity across lifespan. At normal physiological levels, ROS perform important roles as secondary messengers in diverse molecular processes such as regulating neuronal differentiation, polarization, synapse maturation, and neurotransmission. In contrast, high levels of ROS are toxic and can ultimately lead to cell death. Excitable cells, such as neurons, often require high levels of metabolic activity to perform their functions. As a consequence, these cells are more likely to produce high levels of ROS, potentially enhancing their susceptibility to oxidative damage. In addition, because neurons are generally post-mitotic, they may be subject to accumulating oxidative damage. Thus, maintaining tight control over ROS concentration in the nervous system is essential for proper neuronal development and function. We are developing a more complete understanding of the cellular and molecular mechanisms for control of ROS in these processes. This review focuses on ROS regulation of the developmental and functional properties of neurons, highlighting recent in vivo studies. We also discuss the current evidence linking oxidative damage to pathological conditions associated with neurodevelopmental and neurodegenerative disorders.

Keywords: C. elegans; brain injury; neurodegenerative disease; neurodevelopment; oxidative stress; synapse.

Figure 1

Influence of reactive oxygen species in the life of a neuron. Under normal conditions, the diffusible nonradical ROS, hydrogen peroxide, is synthesized physiologically and is a key regulator of processes fundamental to neuronal development and function, including neuronal differentiation, polarization, synaptic maturation, neuropeptide secretion, and neurotransmitter receptor transport. On the other hand, uncontrolled ROS production by damaged mitochondria, especially of superoxide and hydroxyl radicals, are potentially detrimental. Uncontrolled ROS may damage neurons, promote neuronal decline, and exacerbate neurodegenerative pathology. Created with BioRender.com (accessed on 17 February 2022).