About this Research Topic
Neurons are post mitotic cells displaying pronounced vulnerability to oxidative damage. Such a feature depends on a combination of several factors including: i) the composition of cell membranes, which are very rich in polyunsaturated fatty acids and prone to be oxidized; ii) the high concentration of redox-active metals (e.g. Fe and Cu) that, if not properly retained and stored, can easily react with oxygenated species; iii) the production of neurotransmitters – i.e., nitric oxide (NO), glutamate, dopamine – that, directly, or as side effects of their metabolism, generate high levels of reactive oxygen species (ROS). Last, but not least, neurons display a distinctive bioenergetic metabolism, and mitochondrial oxygen consumption rate is particularly elevated to sustain the high ATP (energy) expenditure.
Altogether, these elements contribute to the exquisite sensitivity of the brain, and more in general of the nervous system, to the detrimental effects of oxidative stress. Consistently, altered redox balance is a distinctive sign of many neurodegenerative diseases and – as a result of the accumulation of oxidative damage over the entire lifespan – of all those neurological disorders associated with aging. Additionally, and considered their elevated generation of ROS, alterations of mitochondrial function and dynamics, and defects in their removal by autophagy have been frequently reported as phenomena accompanying the onset and progression of cognitive declines, neurodegeneration, and aging. More recent findings clearly indicate the crucial role of metabolic networks and neuron-glia crosstalk in the regulation of neuronal tolerance against oxidative stress, which may involve specific (unconventional) antioxidant systems to prevent deterioration. Finally, emerging evidence highlights the impact of metabolism and redox signaling on genetic and epigenetic regulation of gene expression. Collectively, these elements indicate the extraordinary complexity of the multi-leveled molecular mechanisms deployed by neurons to cope with oxidative stress.
The aim of this Research Topic is to gather original research and review articles, methods, and commentaries relevant to get new insights into the tight interplay between metabolic adaptation and antioxidant capacity in neuronal cells: How they change and/or are affected during aging, or in the insurgence of neurological and neuromuscular diseases. In particular, we look for contributions that shed light on new redox mechanisms and metabolic networks, including autophagy, which play a role in maintaining neuronal viability or driving, by contrast, neuronal cell death. We are open to articles that provide information on innovative techniques to study, in vitro and in vivo, oxidative stress and metabolic rearrangement of neuronal cells (e.g., damage to biomolecules, live-imaging evaluation and high-throughput screenings of metabolites and free radicals), which occur during aging, neurodegeneration or in pathological conditions affecting the neuromuscular apparatus and the nervous system as a whole. We also welcome articles dealing with new findings about ROS and NO-mediated redox regulation of metabolic enzymes and/or proteins that concur to adapt cellular bioenergetics to the metabolic needs of neuronal cells. This Research Topic is also aimed at elaborating on the role played by mitochondrial metabolism and ROS production in neuronal healthy state. Finally, we encourage studies proposing new potential therapeutic targets for innovative lines of intervention aimed at preventing or treating aging-related neurological and neuromuscular disorders to ultimately improve the quality of life for the increasing number of patients suffering from these devastating diseases.
Important Note: All contributions to this Research Topic must be within the scope of the section and journal to which they are submitted, as defined in their mission statements. Frontiers reserves the right to guide an out-of-scope manuscript to a more suitable section or journal at any stage of peer review.