Impact of N‐Truncated Aβ Peptides on Cu‐ and Cu(Aβ)‐Generated ROS: CuI Matters!
Open accessAbstract
In vitro Cu(Aβ 1–x)‐induced ROS production has been extensively studied. Conversely, the ability of N‐truncated isoforms of Aβ to alter the Cu‐induced ROS production has been overlooked, even though they are main constituents of amyloid plaques found in the human brain. N‐Truncated peptides at the positions 4 and 11 (Aβ 4–x and Aβ 11–x) contain an amino‐terminal copper and nickel (ATCUN) binding motif (H 2 N‐Xxx‐Zzz‐His) that confer them different coordination sites and higher affinities for Cu II compared to the Aβ 1–x peptide. It has further been proposed that the role of Aβ 4–x peptide is to quench Cu II toxicity in the brain. However, the role of Cu I coordination has not been investigated to date. In contrast to Cu II, Cu I coordination is expected to be the same for N‐truncated and N‐intact peptides. Herein, we report in‐depth characterizations and ROS production studies of Cu (Cu I and Cu II) complexes of the Aβ 4–16 and Aβ 11–16 N‐truncated peptides. Our findings show that the N‐truncated peptides do produce ROS when Cu I is present in the medium, albeit to a lesser extent than the unmodified counterpart. In addition, when used as competitor ligands (i.e., in the presence of Aβ 1–16), the N‐truncated peptides are not able to fully preclude Cu(Aβ 1–16)‐induced ROS production.
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Redox inert Cu(II) ATCUN motif is not enough to inhibit ROS production.
“This behavior, showing that redox inert Cu(II) ATCUN motif is not enough to inhibit ROS production, has been previously shown and explained by other authors [57, 58].”
From Semax, a Copper Chelator Peptide, Decreases the Cu(II)-Catalyzed ROS Production and Cytotoxicity of Aβ by Metal Ion Stripping and Redox Silencing (2025) · cites this paper as [57]
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- Authors
- Esmieu, C., Ferrand, G., Borghesani, V., & Hureau, C.
- Affiliations
- Centre National de la Recherche Scientifique (FR)
- Corresponding author
- Esmieu, Charlène
- Hureau, Christelle
- Venue
- Chemistry – A European Journal
- Publisher
- Wiley
- Published
- 2020-12-14
- Volume
- 27
- Issue
- 5
- Pages
- 1777-1786
- ISSN
- 0947-6539 (ISSN-L)
- 1521-3765
- OpenAlex
- W3092978833
- Cited by
- 43
- References
- 0
- Citations by year
- 2026: 3 · 2025: 9 · 2024: 9 · 2023: 3 · 2022: 12 · 2021: 6 · 2020: 1
- FWCI
- 3.31
- Type
- journal article
- Language
- en
- Open access
- green
- hal.science
- Licence
- Locations
- Chemistry - A European Journal (publishedVersion)
- PubMed (publishedVersion)
- HAL (submittedVersion, other-oa)
- Funders
- European Research Council (StG638712)
- FP7 Ideas: European Research Council (PCOFUND-GA-2013-609102)
- Topics
- Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
- Physical Sciences › Chemistry › Inorganic Chemistry › Metal-Catalyzed Oxygenation Mechanisms
- Health Sciences › Medicine › Oncology › Metal complexes synthesis and properties
- Keywords
- amyloid-beta, copper(I) complexes, copper(II) complexes, reactive oxygen species, copper binding, ATCUN motif, amyloid plaques, Alzheimer's disease
- MeSH terms
- Copper, Humans, Peptide Fragments, Amyloid beta-Peptides, Reactive Oxygen Species, Plaque, Amyloid
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