Fig. 8.
Model of Aβ-mediated oxidative stress. CuZn-SOD1 breaks down superoxide free radicals (O2−) in the cytoplasm to produce H2O2 and molecular oxygen (O2). In the presence of oxygen, Fe2+ cycles back to Fe3+ by the Aβ to produce H2O2. H2O2 is neutralized into water by CAT. The heavy chain of ferritin (Fer1HC) has ferroxidase activity, which catalyses the conversion of Fe2+ into Fe3+ ions. Fe3+ is subsequently stored by the light chain of ferritin (Fer2LC). Thus, ferritin has two effects: it prevents Fe2+ from interacting with the Aβ and producing H2O2 and it prevents Fe2+ from reacting with H2O2 and producing the free radical hydroxyl (OH.) via the Fenton reaction. Hydroxyl radicals can also oxidize lipids to generate long-lived reactive aldehydes. Carbonyl reductase (CAR) and GST are downstream antioxidant defences that participate in the detoxification of the reactive aldehyde species.