概要 |
A large amount of energy, in the form of ATP, is required to maintain basic brain functions, such as maintenance or re-establishment of membrane potential, signaling and essential cellular activities.... This ATP is supplied by consuming large amounts of oxygen and glucose via oxidative phosphorylation in mitochondria (MacKenna et al., 2012). However, highly reactive oxygen species (ROS), such as superoxide anions, hydrogen peroxide or hydroxyl radicals, are generated through reduction of oxygens by electrons leaked from the electron transport chain in mitochondria (Kang et al., 1999; Nunnari and Suomalainen, 2012). Reactive nitrogen species (RNS), such as nitric oxide (NO), are physiologically generated upon neural excitation or during the inflammatory responses of glial cells, which are activated during infection or inflammation in the brain. In the presence of superoxide anions, NO can be converted into peroxynitrite, a highly RNS. RO/NS are extremely reactive and attack various biomolecules, such as lipids, proteins, carbohydrates, and nucleic acids. This outcome induces various chemical modifications in these molecules, including oxidation, nitration, S-nitrosylation, deamination, and glutathionylation (Cobb and Cole, 2015). There are many defense mechanisms that minimize the toxic effects of RO/NS, including antioxidant enzymes, such as superoxide dismutase (SOD), catalase and glutathione peroxidase; however, the brain is constantly exposed to endogenous RO/NS produced during normal brain functions (Dasuri et al., 2013).続きを見る
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