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

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• 作者：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
• 刊名：Journal of the American Chemical Society
• 出版年：2016
• 出版时间：March 30, 2016
• 年：2016
• 卷：138
• 期：12
• 页码：3966-3969
• 全文大小：315K
• ISSN：1520-5126

文摘

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.