Are reactive oxygen species involved in Alzheimer's disease?
Alzheimer's disease has a multifactorial pathogenesis. Among the various factors involved, this review examines, in particular, the possibility of oxidative stress, meaning an imbalance between the formation and spread of reactive oxygen species (ROS) and the antioxidant defenses. This theory is supported by the following observations: (a) the alteration of mitochondrial function, which is likely to lead to the electron leakage in the respiratory chain and the consequent formation of superoxide radicals; (b) the unbalanced high activity of superoxide dismutase and monoamine oxidase B which causes the production of more H2O2; (c) the alteration of iron homeostasis which, in combination with the superoxide and H2O2, gives rise to the most deleterious hydroxyl radicals; (d) the increased lipid peroxidation and membrane alterations; (e) the pro-aggregating effect of ROS on beta/A4 protein and the C-terminal fragment of amyloid precursor (A4CT). Most of these changes are already present in the normal aging brain but are aggravated in AD presumably over a number of years. However, further investigations are needed to confirm these theories particularly regarding the alterations of another target of ROS, the proteins. Peroxidative stress is presumably present in the AD brain. This stress might not be a primary factor in the pathogenesis of AD, but a consequence of the tissue injury. In any case, it could contribute considerably to the pathology, in a vicious cycle of actions and reactions resulting in a critical mass of metabolic errors, responsible in the end for this disease.
Institute of Pharmacology, Faculty of Science, University of Pavia, Italy.
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Benzi
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Moretti
D000544:Alzheimer Disease / Q000378:metabolism*; D000682:Amyloid / Q000378:metabolism; D001921:Brain / Q000378:metabolism; D004249:DNA Damage; D004579:Electron Transport; D005609:Free Radicals; D005978:Glutathione / Q000378:metabolism; D006801:Humans; D007501:Iron / Q000502:physiology; D015227:Lipid Peroxidation; D008928:Mitochondria / Q000378:metabolism; D018384:Oxidative Stress; D017382:Reactive Oxygen Species / Q000378:metabolism*; D013482:Superoxide Dismutase / Q000502:physiology; D013481:Superoxides / Q000378:metabolism
D000682:Amyloid; D005609:Free Radicals; D017382:Reactive Oxygen Species; D013481:Superoxides; D007501:Iron; D013482:Superoxide Dismutase; D005978:Glutathione