Amyloid-β and α-Synuclein Decrease the Level of Metal-Catalyzed Reactive Oxygen Species by Radical Scavenging and Redox Silencing

Jeppe T Pedersen, Serene W Chen, Christian B Borg, Samuel Ness, Justyna M. Bahl, Niels H H Heegaard, Christopher M Dobson, Lars Hemmingsen, Nunilo Cremades, Kaare Teilum

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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.

Original languageEnglish
JournalAmerican Chemical Society. Journal
Volume138
Issue number12
Pages (from-to)3966–3969
ISSN0002-7863
DOIs
Publication statusPublished - 20. Apr 2016

Keywords

  • Journal Article
  • Research Support, Non-U.S. Gov't

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