Amyloid-β and α-Synuclein Decrease the Level of Metal-Catalyzed Reactive Oxygen Species by Radical Scavenging and Redox Silencing
| Autor: | Lars Hemmingsen, Jeppe T. Pedersen, Kaare Teilum, Nunilo Cremades, Serene W. Chen, Samuel Ness, Justyna M.C. Bahl, Niels H. H. Heegaard, Christian B. Borg, Christopher M. Dobson |
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| Přispěvatelé: | Apollo - University of Cambridge Repository, Villum Fonden, Lundbeck Foundation, Agency for Science, Technology and Research A*STAR (Singapore), Wellcome Trust, Ministerio de Economía y Competitividad (España) |
| Jazyk: | angličtina |
| Rok vydání: | 2016 |
| Předmět: |
Amyloid
010402 general chemistry 01 natural sciences Biochemistry Redox Catalysis Pathogenesis Metal chemistry.chemical_compound Colloid and Surface Chemistry Journal Article Gene silencing Organic chemistry Humans chemistry.chemical_classification Alpha-synuclein Reactive oxygen species Amyloid beta-Peptides 010405 organic chemistry Communication Research Support Non-U.S. Gov't General Chemistry Free Radical Scavengers In vitro 0104 chemical sciences 3. Good health chemistry visual_art visual_art.visual_art_medium Biophysics alpha-Synuclein Reactive Oxygen Species Oxidation-Reduction Copper |
| Zdroj: | Pedersen, J T, Chen, S W, Borg, C B, Ness, S, Bahl, J M, Heegard, N H H, Dobson, C M, Hemmingsen, L B S, Cremades, N & Teilum, K 2016, ' Amyloid-β and α-synuclein decrease the level of metal-catalyzed reactive oxygen species by radical scavenging and redox silencing ', Journal of the American Chemical Society, vol. 138, no. 12, pp. 3966-3969 . https://doi.org/10.1021/jacs.5b13577 Digital.CSIC. Repositorio Institucional del CSIC instname Pedersen, J T, Chen, S W, Borg, C B, Ness, S, Bahl, J M, Heegaard, N H H, Dobson, C M, Hemmingsen, L, Cremades, N & Teilum, K 2016, ' Amyloid-β and α-Synuclein Decrease the Level of Metal-Catalyzed Reactive Oxygen Species by Radical Scavenging and Redox Silencing ', American Chemical Society. Journal, vol. 138, no. 12, pp. 3966–3969 . https://doi.org/10.1021/jacs.5b13577 Journal of the American Chemical Society |
| DOI: | 10.1021/jacs.5b13577 |
| Popis: | 4 pags, 3 figs. -- The Supporting Information is available free of charge on the ACS Publications website at DOI: 10.1021/jacs.5b13577 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 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 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 Cu2+ and other ROS-active metal ions in the aggregates or as a downstream consequence of the formation of the pathological amyloid structures. This work was supported by the Villum Foundation (J.T.P., L.H.), the Lundbeck Foundation (J.T.P., K.T.), the Agency for Science, Technology and Research, Singapore (S.W.C.), The Wellcome Trust (C.M.D.) and the Spanish Ministry of Economy and Competitiveness through the Ramon y Cajal program (N.C.). |
| Databáze: | OpenAIRE |
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