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Amyloid-β and α-Synuclein Decrease the Level of Metal-Catalyzed Reactive Oxygen Species by Radical Scavenging and Redox Silencing
[Image: see text] 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...
Autores principales: | , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
American Chemical
Society
2016
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Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4827876/ https://www.ncbi.nlm.nih.gov/pubmed/26967463 http://dx.doi.org/10.1021/jacs.5b13577 |
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author | Pedersen, Jeppe T. Chen, Serene W. Borg, Christian B. Ness, Samuel Bahl, Justyna M. Heegaard, Niels H. H. Dobson, Christopher M. Hemmingsen, Lars Cremades, Nunilo Teilum, Kaare |
author_facet | Pedersen, Jeppe T. Chen, Serene W. Borg, Christian B. Ness, Samuel Bahl, Justyna M. Heegaard, Niels H. H. Dobson, Christopher M. Hemmingsen, Lars Cremades, Nunilo Teilum, Kaare |
author_sort | Pedersen, Jeppe T. |
collection | PubMed |
description | [Image: see text] 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. |
format | Online Article Text |
id | pubmed-4827876 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2016 |
publisher | American Chemical
Society |
record_format | MEDLINE/PubMed |
spelling | pubmed-48278762016-04-12 Amyloid-β and α-Synuclein Decrease the Level of Metal-Catalyzed Reactive Oxygen Species by Radical Scavenging and Redox Silencing Pedersen, Jeppe T. Chen, Serene W. Borg, Christian B. Ness, Samuel Bahl, Justyna M. Heegaard, Niels H. H. Dobson, Christopher M. Hemmingsen, Lars Cremades, Nunilo Teilum, Kaare J Am Chem Soc [Image: see text] 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. American Chemical Society 2016-03-11 2016-03-30 /pmc/articles/PMC4827876/ /pubmed/26967463 http://dx.doi.org/10.1021/jacs.5b13577 Text en Copyright © 2016 American Chemical Society This is an open access article published under a Creative Commons Attribution (CC-BY) License (http://pubs.acs.org/page/policy/authorchoice_ccby_termsofuse.html) , which permits unrestricted use, distribution and reproduction in any medium, provided the author and source are cited. |
spellingShingle | Pedersen, Jeppe T. Chen, Serene W. Borg, Christian B. Ness, Samuel Bahl, Justyna M. Heegaard, Niels H. H. Dobson, Christopher M. Hemmingsen, Lars Cremades, Nunilo Teilum, Kaare Amyloid-β and α-Synuclein Decrease the Level of Metal-Catalyzed Reactive Oxygen Species by Radical Scavenging and Redox Silencing |
title | Amyloid-β
and α-Synuclein
Decrease the Level of Metal-Catalyzed Reactive Oxygen Species by Radical
Scavenging and Redox Silencing |
title_full | Amyloid-β
and α-Synuclein
Decrease the Level of Metal-Catalyzed Reactive Oxygen Species by Radical
Scavenging and Redox Silencing |
title_fullStr | Amyloid-β
and α-Synuclein
Decrease the Level of Metal-Catalyzed Reactive Oxygen Species by Radical
Scavenging and Redox Silencing |
title_full_unstemmed | Amyloid-β
and α-Synuclein
Decrease the Level of Metal-Catalyzed Reactive Oxygen Species by Radical
Scavenging and Redox Silencing |
title_short | Amyloid-β
and α-Synuclein
Decrease the Level of Metal-Catalyzed Reactive Oxygen Species by Radical
Scavenging and Redox Silencing |
title_sort | amyloid-β
and α-synuclein
decrease the level of metal-catalyzed reactive oxygen species by radical
scavenging and redox silencing |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4827876/ https://www.ncbi.nlm.nih.gov/pubmed/26967463 http://dx.doi.org/10.1021/jacs.5b13577 |
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