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The antioxidant system of CNS Two major types of antioxidant response are exist in the CNS: the non‐enzymatic antioxidant system and the enzymatic antioxidant system.69, 147 The enzyme antioxidant system mainly includes several antioxidant enzymes such as glutathione peroxidase (GPxs), superoxide dismutase (SODs), catalase (CATs) and peroxidase (Prxs), and some phase II reaction enzymes, such as haeme oxygenase 1 (HO‐1), reduced coenzyme/quinone oxidoreductase 1 (NQO1) and γ‐glutamylcysteine acid ligase (GCLC).147 Nuclear factor erythroid 2‐related factor 2 (Nrf2) is an important transcription factor involved in maintenance of redox and metabolic homeostasis by regulating the expression of various antioxidant enzymes.22 Non‐enzymatic antioxidant systems include a variety of endogenous reducing substances, such as vitamin C, vitamin E, glutathione (GSH), NADPH, uric acid, bilirubin and melatonin, playing crucial role in ROS scavenging.13, 147 Besides, the thioredoxin (Trx) system is another non‐enzymatic antioxidant system in the CNS89, 100 and it acts as an antioxidant through the reversible oxidation‐reduction reaction between the active site of cysteine in Trx and NADPH.82 3

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