title: Amyloid-β and α-Synuclein Decrease the Level of Metal-Catalyzed Reactive Oxygen Species by Radical Scavenging and Redox Silencing.
abstract: The formation of reactive oxygen species (ROS) is linked to the pathogenesis of neurodegenerative diseases. Here we have investigated the effect of soluble and aggregated amyloid-β (Aβ) and α-synuclein (αS), associated with Alzheimer's and Parkinson's diseases, respectively, on the Cu(2+)-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 Cu(2+) is bound to Aβ or αS, 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 Aβ or αS does not result from a particularly ROS-active form of these peptides, but rather from either a local increase of Cu(2+) and other ROS-active metal ions in the aggregates or as a downstream consequence of the formation of the pathological amyloid structures.
authors.forename: Jeppe T
authors.initials: JT
authors.lastname: Pedersen
authors.affiliation: Department of Chemistry, University of Cambridge , Lensfield Road, Cambridge CB2 1EW, United Kingdom.
authors.forename: Serene W
authors.initials: SW
authors.lastname: Chen
authors.affiliation: Department of Biology, University of Copenhagen , 2200 Copenhagen, Denmark.
authors.forename: Christian B
authors.initials: CB
authors.lastname: Borg
authors.affiliation: Department of Chemistry, University of Cambridge , Lensfield Road, Cambridge CB2 1EW, United Kingdom.
authors.forename: Samuel
authors.initials: S
authors.lastname: Ness
authors.affiliation: Department of Autoimmunology and Biomarkers, Statens Serum Institut , 2300 Copenhagen, Denmark.|Department of Clinical Biochemistry, Clinical Institute, Odense University Hospital, University of Southern Denmark , 5000 Odense, Denmark.
authors.forename: Justyna M
authors.initials: JM
authors.lastname: Bahl
authors.affiliation: Department of Autoimmunology and Biomarkers, Statens Serum Institut , 2300 Copenhagen, Denmark.|Department of Clinical Biochemistry, Clinical Institute, Odense University Hospital, University of Southern Denmark , 5000 Odense, Denmark.
authors.forename: Niels H H
authors.initials: NH
authors.lastname: Heegaard
authors.affiliation: Department of Chemistry, University of Cambridge , Lensfield Road, Cambridge CB2 1EW, United Kingdom.
authors.forename: Christopher M
authors.initials: CM
authors.lastname: Dobson
authors.forename: Lars
authors.initials: L
authors.lastname: Hemmingsen
authors.affiliation: Department of Chemistry, University of Cambridge , Lensfield Road, Cambridge CB2 1EW, United Kingdom.|Biocomputation and Complex Systems Physics Institute (BIFI)-Joint Unit BIFI-IQFR (CSIC), University of Zaragoza , 50018 Zaragoza, Spain.
authors.forename: Nunilo
authors.initials: N
authors.lastname: Cremades
authors.affiliation: Department of Biology, University of Copenhagen , 2200 Copenhagen, Denmark.
authors.forename: Kaare
authors.initials: K
authors.lastname: Teilum
mesh_terms: D016229:Amyloid beta-Peptides / Q000378:metabolism*; D002384:Catalysis; D003300:Copper / Q000737:chemistry*; D016166:Free Radical Scavengers / Q000378:metabolism; D006801:Humans; D010084:Oxidation-Reduction; D017382:Reactive Oxygen Species / Q000378:metabolism; D051844:alpha-Synuclein / Q000378:metabolism*
chemical_list: D016229:Amyloid beta-Peptides; D016166:Free Radical Scavengers; D017382:Reactive Oxygen Species; D051844:alpha-Synuclein; D003300:Copper