Amyloid-β and α-synuclein decrease the level of metal-catalyzed reactive oxygen species by radical scavenging and redox silencing

Jeppe Trudslev Pedersen; Serene W. Chen; Christian Bernsen Borg; Samuel Ness; Justyna M. Bahl; Niels H. H. Heegard; Christopher M. Dobson; Lars Bo Stegeager Hemmingsen; Nunilo Cremades; Kaare Teilum

doi:10.1021/jacs.5b13577

Amyloid-β and α-synuclein decrease the level of metal-catalyzed reactive oxygen species by radical scavenging and redox silencing

Jeppe Trudslev Pedersen, Serene W. Chen, Christian Bernsen Borg, Samuel Ness, Justyna M. Bahl, Niels H. H. Heegard, Christopher M. Dobson, Lars Bo Stegeager 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 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.

Original language	English
Journal	Journal of the American Chemical Society
Volume	138
Issue number	12
Pages (from-to)	3966-3969
Number of pages	4
ISSN	0002-7863
DOIs	https://doi.org/10.1021/jacs.5b13577
Publication status	Published - 20 Apr 2016

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Pedersen_2016_amyloid-beta_andFinal published version, 1.04 MBLicence: CC BY

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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, 138(12), 3966-3969. https://doi.org/10.1021/jacs.5b13577

Amyloid-β and α-synuclein decrease the level of metal-catalyzed reactive oxygen species by radical scavenging and redox silencing. / Pedersen, Jeppe Trudslev; Chen, Serene W.; Borg, Christian Bernsen et al.
In: Journal of the American Chemical Society, Vol. 138, No. 12, 20.04.2016, p. 3966-3969.

Research output: Contribution to journal › Journal article › Research › peer-review

Pedersen, JT, Chen, SW, Borg, CB, Ness, S, Bahl, JM, Heegard, NHH, Dobson, CM, Hemmingsen, LBS, 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

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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 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.",

author = "Pedersen, {Jeppe Trudslev} and Chen, {Serene W.} and Borg, {Christian Bernsen} and Samuel Ness and Bahl, {Justyna M.} and Heegard, {Niels H. H.} and Dobson, {Christopher M.} and Hemmingsen, {Lars Bo Stegeager} and Nunilo Cremades and Kaare Teilum",

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T1 - Amyloid-β and α-synuclein decrease the level of metal-catalyzed reactive oxygen species by radical scavenging and redox silencing

AU - Pedersen, Jeppe Trudslev

AU - Chen, Serene W.

AU - Borg, Christian Bernsen

AU - Ness, Samuel

AU - Bahl, Justyna M.

AU - Heegard, Niels H. H.

AU - Dobson, Christopher M.

AU - Hemmingsen, Lars Bo Stegeager

AU - Cremades, Nunilo

AU - Teilum, Kaare

PY - 2016/4/20

Y1 - 2016/4/20

N2 - 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.

AB - 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.

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EP - 3969

JO - Journal of the American Chemical Society

JF - Journal of the American Chemical Society

IS - 12

ER -

Amyloid-β and α-synuclein decrease the level of metal-catalyzed reactive oxygen species by radical scavenging and redox silencing

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