Decrease in peptide methionine sulfoxide reductase in Alzheimer's disease brain

Previous studies have shown that the pathophysiology of Alzheimer's disease (AD) is linked to oxidative stress. Oxidative damage to different biomolec ular components of the brain is a characteristic feature of AD. Recent evid ence suggests that methionine may act as an antioxidant defense molecule in proteins by its ability to scavenge oxidants and, in the process, undergo oxidation to form methionine sulfoxide, The enzyme peptide, methionine sulf oxide reductase (MsrA), reverses methionine sulfoxide back to methionine, w hich once again is able to scavenge oxidants, The purpose of this study was to measure the activity of MsrA in the brain of AD patients compared with control subjects. Our results showed that there was a decline in MsrA activ ity in all brain regions studied in AD and this decline reached statistical significance in the superior and middle temporal gyri (p < 0.001), inferio r parietal lobule (p < 0.05), and the hippocampus(p < 0.05) in AD. An eleva tion of protein carbonyl content was found in all brain regions except the cerebellum in AD and reached statistical significance in the superior and m iddle temporal gyri and hippocampus. Messenger RNA analysis suggests that t he loss in enzyme activity may be the result of a posttranslational modific ation of MsrA or a defect of translation resulting in inferior processing o f the MsrA mRNA. Our results suggest that a decline in MsrA activity could reduce the antioxidant defenses and increase the oxidation of critical prot eins in neurons in the brain in AD.