Amyloid-β Binds Cu 2+ in a Mononuclear Metal Ion Binding Site
Abstract
Amyloid-beta (Abeta) peptide is the principal constituent of plaques associated with Alzheimer's disease and is thought to be responsible for the neurotoxicity associated with the disease. Metal ions have been hypothesized to play a role in the formation and neurotoxicity of aggregates associated with Alzheimer's disease (Bush, A. I.; et al. Proc. Natl. Acad. Sci. U.S.A. 2003, 100, 11934). Elucidation of the chemistry through which transition-metal ions participate in the assembly and toxicity of Abeta oligomers is important to drug design efforts if inhibition of Abeta containing bound metal ions becomes a treatment for Alzheimer's disease. In this paper, we report electron paramagnetic resonance (EPR) spectroscopic characterization of Cu(2+) bound to soluble and fibrillar Abeta. Addition of stoichiometric amounts of Cu(2+) to soluble Abeta produces an EPR signal at 10 K with observable Cu(2+) hyperfine lines. A nearly identical spectrum is observed for Abetafibrils assembled in the presence of Cu(2+). The EPR parameters are consistent with a Type 2 Cu(2+) center with three nitrogen donor atoms and one oxygen donor atom in the coordination sphere of Cu(2+): g( parallel) = 2.26 and A( parallel) = 174 +/- 4 G for soluble Abeta with Cu(2+), and g( parallel) = 2.26 and A( parallel) = 175 +/- 1 G for Abeta fibrils assembled with Cu(2+). Investigation of the temperature dependence of the EPR signal for Cu(2+) bound to soluble Abetaor Cu(2+) in fibrillar Abeta shows that the Cu(2+)…
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These metal ions have been shown to promote Aβ40 aggregation.
“Thus, these metal ions have been shown to promote Aβ40 aggregation,23–27,29–32”
From Bifunctional Compounds for Controlling Metal-Mediated Aggregation of the Aβ<sub>42</sub>Peptide (2012) · cites this paper as [32]
This is in contrast with a large number of reports showing the aggregation-promoting effect of metal ions on the Aβ peptide.
“This is in contrast with a large number of reports showing the aggregation-promoting effect of metal ions on the Aβ peptide.23–27,29–32,37,38”
From Bifunctional Compounds for Controlling Metal-Mediated Aggregation of the Aβ<sub>42</sub>Peptide (2012) · cites this paper as [32]
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- Authors
- Karr, J. W., Kaupp, L. J., & Szalai, V. A.
- Affiliations
- University of Maryland, Baltimore County (US)
- ORCID
- Szalai, Veronika A.
- Venue
- Journal of the American Chemical Society
- Publisher
- American Chemical Society (ACS)
- Published
- 2004-09-23
- Volume
- 126
- Issue
- 41
- Pages
- 13534-13538
- ISSN
- 0002-7863 (ISSN-L)
- 1520-5126
- OpenAlex
- W2075420978
- Cited by
- 160
- References
- 6
- Citations by year
- 2026: 2 · 2025: 5 · 2024: 5 · 2023: 1 · 2022: 2 · 2021: 2 · 2020: 2 · 2019: 1 · 2018: 5 · 2017: 4 · 2016: 5 · 2015: 6 · 2014: 5 · 2013: 10 · 2012: 17
- FWCI
- 5.63
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Journal of the American Chemical Society (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Biophysics › Electron Spin Resonance Studies
- Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
- Keywords
- amyloid-beta, copper(II) binding, Alzheimer's disease, metal ion binding, amyloid fibrils, Curie behavior, antiferromagnetic coupling, peptide aggregation, neurotoxicity
- MeSH terms
- Binding Sites, Cations, Divalent, Cold Temperature, Copper, Electron Spin Resonance Spectroscopy, Organometallic Compounds, Peptide Fragments, Protein Binding, Amyloid beta-Peptides
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