Regarding the role(s) of metformin in CNS, our group showed that metformin protects T2D rat brain against oxidative stress [e.g., thiobarbituric acid reactive substances (Figure 1) and malondialdehyde levels], probably by inhibiting the antioxidant enzymes glutathione peroxidase (GPx) and glutathione reductase (GRed), by improving the levels of the non-enzymatic antioxidant glutathione (GSH) and by stimulating manganese superoxide dismutase (MnSOD) activity (65). The gene discussed is SOD2; the disease is type 2 diabetes mellitus.