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Here we have investigated the effect of soluble and aggregated amyloid-\u03b2 (A\u03b2) and \u03b1-synuclein (\u03b1S), associated with Alzheimer\u2019s and Parkinson\u2019s diseases, respectively, on the Cu2+-catalyzed formation of ROS in vitro in the presence of a biological reductant. We find that the levels of ROS, and the rate by which ROS is generated, are significantly reduced when Cu2+ is bound to A\u03b2 or \u03b1S, particularly when they are in their oligomeric or fibrillar forms. This effect is attributed to a combination of radical scavenging and redox silencing mechanisms. Our findings suggest that the increase in ROS associated with the accumulation of aggregated A\u03b2 or \u03b1S does not result from a particularly ROS-active form of these peptides, but rather from either a local increase of Cu2+ and other ROS-active metal ions in the aggregates or as a downstream consequence of the formation of the pathological amyloid structures.<\/jats:p>","DOI":"10.1021\/jacs.5b13577","type":"journal-article","created":{"date-parts":[[2016,3,11]],"date-time":"2016-03-11T11:39:00Z","timestamp":1457696340000},"page":"3966-3969","source":"Crossref","is-referenced-by-count":80,"title":["Amyloid-\u03b2\nand \u03b1-Synuclein\nDecrease the Level of Metal-Catalyzed Reactive Oxygen Species by Radical\nScavenging and Redox Silencing"],"prefix":"10.1021","volume":"138","author":[{"given":"Jeppe T.","family":"Pedersen","sequence":"first","affiliation":[{"name":"University of Copenhagen , , ,","place":["Copenhagen, Denmark, 2100"]},{"name":"University of Copenhagen , , ,","place":["Copenhagen, Denmark, 2100"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Serene W.","family":"Chen","sequence":"additional","affiliation":[{"name":"University of Cambridge , , Lensfield Road , ,","place":["Cambridge, United Kingdom, CB2 1EW"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christian B.","family":"Borg","sequence":"additional","affiliation":[{"name":"University of Copenhagen , , ,","place":["Copenhagen, Denmark, 2200"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Samuel","family":"Ness","sequence":"additional","affiliation":[{"name":"University of Cambridge , , Lensfield Road , ,","place":["Cambridge, United Kingdom, CB2 1EW"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Justyna M.","family":"Bahl","sequence":"additional","affiliation":[{"name":"Statens Serum Institut , , ,","place":["Copenhagen, Denmark, 2300"]},{"name":"Odense University Hospital, University of Southern Denmark , , ,","place":["Odense, Denmark, 5000"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Niels H. 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