**4. Conclusions**

Brains are metabolically active and have a high demand for large amounts of ATP to maintain their physiological function. Additionally, the brain has a relatively low level of antioxidants, low repair capacity, non-replicating nature of neuronal cells, and a high ratio of membrane surface to cytoplasm. ROS production is largely through oxidative phosphorylation and increased free radicals play a central role in neurological disorders by the imbalance of pro-oxidant and antioxidant agents in the brain. This underpins the importance of targeting antioxidant systems to counteract the oxidative stress and associated brain diseases. Indeed, the antioxidant system is important for the rescue of neuronal cells from oxidative stress and preservation of the right redox balance in the brain tissue by promoting antioxidative defenses for neutralizing ROS and by blocking transcription. Currently, there is growing research interest in the development of new/combination exogenous supplementation of antioxidants, retention of the functional integrity of intrinsic antioxidant systems for preventing harmful CNS disorders, and identification of novel approaches to therapy to prevent and/or reduce brain injury. Thus, high levels and variable metabolites in the brain indicate an increased requirement for antioxidant defense systems as enzymatic and non-enzymatic molecules. Redox biology fulfills important physiological functions that extend beyond its role on oxidative stress, such as cell signaling [210,211]. Perhaps, ROS generation may be necessary for cell function. Although their role is still ill-defined, the antioxidant systems may contribute to the controlled release of ROS for normal brain function.

**Author Contributions:** All authors contributed substantially to the preparation of this study. K.H.L. designed the study and drafted the manuscript. M.C. assisted with drafting of the manuscript and preparation of the figures. B.H.L. supervised the entire project and prepared the manuscript draft. All authors have read and agreed to the published version of the manuscript.

**Funding:** This work was supported by the Basic Science Research Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Education (MOE) (NRF-2016R1D1A3B2008194).

**Conflicts of Interest:** The authors declare no conflict of interest.
