Oxidative stress in Alzheimer's disease Ved Chauhan, Abha Chauhan Pathophysiology Volume 13, Issue 3, Pages 195-208 (August 2006) DOI: 10.1016/j.pathophys.2006.05.004 Copyright © 2006 Elsevier Ireland Ltd Terms and Conditions
Fig. 1 Possible mechanism of oxidative stress in AD. Under normal conditions, ROS are neutralized by the action of the ROS defense system (A). When production of ROS overpowers its defense mechanism in AD as a result of aging, increased production of Aβ and its fibrillized form, NFT pathology, and mitochondrial abnormalities, an imbalance is created that results in oxidative stress (B). Pathophysiology 2006 13, 195-208DOI: (10.1016/j.pathophys.2006.05.004) Copyright © 2006 Elsevier Ireland Ltd Terms and Conditions
Fig. 2 Generation of ROS and the cellular defense against them. Oxygen (O2) reacts with the electrons (e) released from respiratory chain reactions, resulting in the formation of oxygen-based free radical (O−2, superoxide), which is converted to hydrogen peroxide (H2O2) by the action of superoxide dismutase (SOD). H2O2 is a powerful oxidizing agent that reacts with metal cations such as ferrous ions (Fe2+), and produces highly reactive hydroxyl radicals (OH). On the defensive end, H2O2 can be neutralized by the action of glutathione peroxidase/catalase, or it can engage in the production of singlet oxygen by the action of myeloperoxidase. Superoxide radical can also cross-react with nitric oxide (NO) and produce NO2-based free radicals. Pathophysiology 2006 13, 195-208DOI: (10.1016/j.pathophys.2006.05.004) Copyright © 2006 Elsevier Ireland Ltd Terms and Conditions
Fig. 3 Possible involvement of aging, mitochondria, head injury, APP, Aβ, and NFT in oxidative stress-induced cell death in AD. Head trauma and aging can induce production of ROS. On the other hand, ROS may activate the β- and γ-secretases to increase Aβ production from APP. Aβ and APP may also directly induce the production of ROS. Aβ can also induce the mitochondrial abnormalities which further increase the production of ROS. These ROS react with lipids, proteins, and nucleic acids and lead to cell death in AD. ROS may also activate protein kinases, leading to tau phosphorylation and NFT pathology, which in turn produce more ROS and result in cellular death. Pathophysiology 2006 13, 195-208DOI: (10.1016/j.pathophys.2006.05.004) Copyright © 2006 Elsevier Ireland Ltd Terms and Conditions
Fig. 4 Hypothetical model linking oxidative stress and acidic membrane lipids with Aβ fibrillization. Acidic lipids such as phosphatidylserine (PS, ●) are localized on the cytoplasmic side of the membrane. Oxidative stress facilitates the flip-flop of PS to the external side of the membrane, thus exposing it to the Aβ molecules. Aβ and PS make heterogeneous nuclei on the surface of the membrane that trigger the fibrillization process of Aβ. Pathophysiology 2006 13, 195-208DOI: (10.1016/j.pathophys.2006.05.004) Copyright © 2006 Elsevier Ireland Ltd Terms and Conditions