13 reasons why the brain is susceptible to oxidative stress

By J. Cobley, Maria Luisa Fiorello, D. Bailey. Redox Biology, 2018

1,008 citations recorded by the source corpus.

The human brain consumes 20% of the total basal oxygen (O2) budget to support ATP intensive neuronal activity. Without sufficient O2 to support ATP demands, neuronal activity fails, such that, even transient ischemia is neurodegenerative. While the essentiality of O2 to brain function is clear, how oxidative stress causes neurodegeneration is ambiguous. Ambiguity exists because many of the reasons why the brain is susceptible to oxidative stress remain obscure. Many are erroneously understood as the deleterious result of adventitious O2 derived free radical and non-radical species generation. To understand how many reasons underpin oxidative stress, one must first re-cast free radical and non-radical species in a positive light because their deliberate generation enables the brain to achieve critical functions (e.g. synaptic plasticity) through redox signalling (i.e. positive functionality). Using free radicals and non-radical derivatives to signal sensitises the brain to oxidative stress when redox signalling goes awry (i.e. negative functionality). To advance mechanistic understanding, we rationalise 13 reasons why the brain is susceptible to oxidative stress. Key reasons include inter alia unsaturated lipid enrichment, mitochondria, calcium, glutamate, modest antioxidant defence, redox active transition metals and neurotransmitter auto-oxidation. We review RNA oxidation as an underappreciated cause of oxidative stress. The complex interplay between each reason dictates neuronal susceptibility to oxidative stress in a dynamic context and neural identity dependent manner. Our discourse sets the stage for investigators to interrogate the biochemical basis of oxidative stress in the brain in health and disease.

Subfields: Molecular Biology, Nutrition and Dietetics, Physiology

View Paper: https://www.semanticscholar.org/paper/9cd8c8b7f661609b68fdc6a83a382db211cd2a55

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In Molecular Biology

1. I. Peluso
2. P. Oliver
3. M. Iriti

In Nutrition and Dietetics

1. Dominic S A Simpson
2. I. Peluso
3. P. Oliver
4. M. Iriti

In Physiology

1. Dominic S A Simpson
2. I. Peluso
3. P. Oliver
4. M. Iriti

Citations in the corpus

• Lifestyle, Oxidative Stress, and Antioxidants: Back and Forth in the Pathophysiology of Chronic Diseases (2020, background): “The excessive use of glucose for energy production makes the brain especially susceptible to oxidative stress, and mitochondrial ETC is the primary ROS source (Cobley et al., 2018).”
• ROS Generation in Microglia: Understanding Oxidative Stress and Inflammation in Neurodegenerative Disease (2020, background): “The brain is particularly susceptible to oxidative stress due to a triad of elevated ROS production, modest antioxidant defences and a limited capacity for regeneration [39].”