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Neurons are especially vulnerable to oxidative stress and accumulation of oxidative damage due to: (1) high brain O 2 concentration, (2) the large metabolic demand of neurons influencing mitochondrial ROS production 41,42 (3) the elevated concentration of polyunsaturated fatty acids in neuronal membranes which are vulnerable to lipid peroxidation, (4) the low ratio of antioxidant to pro-oxidant enzymes in the brain 43,44 , (5) high brain iron content 45 which can contribute to ROS production via the Fenton reaction 44 , and (6) the reliance on error-prone DNA repair pathways such as non-homologous end joining (NHEJ) in place of replication-associated DNA repair 34,41