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Cu(II) Potentiation of Alzheimer Aβ Neurotoxicity
Open accessAbstract
Oxidative stress markers as well as high concentrations of copper are found in the vicinity of Abeta amyloid deposits in Alzheimer's disease. The neurotoxicity of Abeta in cell culture has been linked to H(2)O(2) generation by an unknown mechanism. We now report that Cu(II) markedly potentiates the neurotoxicity exhibited by Abeta in cell culture. The potentiation of toxicity is greatest for Abeta1-42 > Abeta1-40 >> mouse/rat Abeta1-40, corresponding to their relative capacities to reduce Cu(II) to Cu(I), form H(2)O(2) in cell-free assays and to exhibit amyloid pathology. The copper complex of Abeta1-42 has a highly positive formal reduction potential ( approximately +500-550 mV versus Ag/AgCl) characteristic of strongly reducing cuproproteins. These findings suggest that certain redox active metal ions may be important in exacerbating and perhaps facilitating Abeta-mediated oxidative damage in Alzheimer's disease.
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“Since metal-Aβ species have been shown to be neurotoxic,25,51,92”
From Bifunctional Compounds for Controlling Metal-Mediated Aggregation of the Aβ42Peptide (2012) · cites this paper as [92]
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“Because Cu2+–Aβ species have been shown to be neurotoxic,20,21,31,51,52”
From Small Bifunctional Chelators That Do Not Disaggregate Amyloid β Fibrils Exhibit Reduced Cellular Toxicity (2014) · cites this paper as [52]
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Metadata
- Authors
- Huang, X., Cuajungco, M. P., Atwood, C. S., Hartshorn, M. A., Tyndall, J. D. A., Hanson, G. R., Stokes, K. C., Leopold, M., Multhaup, G., Goldstein, L. E., Scarpa, R. C., Saunders, A. J., Lim, J., Moir, R. D., Glabe, C., Bowden, E. F., Masters, C. L., Fairlie, D. P., Tanzi, R. E., & Bush, A. I.
- Affiliations
- Harvard University (US)
- The University of Queensland (AU)
- North Carolina State University (US)
- Heidelberg University (DE)
- University of California, Irvine (US)
- Mental Health Research Institute (AU)
- Corresponding author
- Bush, Ashley I.
- ORCID
- Venue
- Journal of Biological Chemistry
- Publisher
- Elsevier BV
- Published
- 1999-12
- Volume
- 274
- Issue
- 52
- Pages
- 37111-37116
- ISSN
- 0021-9258 (ISSN-L)
- OpenAlex
- W2131633241
- Cited by
- 762
- References
- 40
- Citations by year
- 2026: 9 · 2025: 9 · 2024: 13 · 2023: 14 · 2022: 14 · 2021: 10 · 2020: 15 · 2019: 30 · 2018: 16 · 2017: 19 · 2016: 26 · 2015: 27 · 2014: 33 · 2013: 28 · 2012: 42
- FWCI
- 14.38
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Journal of Biological Chemistry (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Funders
- Massachusetts General Hospital
- Commonwealth of Massachusetts
- National Institutes of Health
- Medical Research Council
- Australian Research Council
- National Health and Medical Research Council
- National Institute on Aging
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Alzheimer's disease research and treatments
- Health Sciences › Nursing › Nutrition and Dietetics › Trace Elements in Health
- Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
- Keywords
- Alzheimer's disease, amyloid-beta, copper(II), neurotoxicity, oxidative stress, hydrogen peroxide production, amyloid-beta 42, Aβ40, copper proteins, metal ions, redox-active metals, oxidative damage
- MeSH terms
- Animals, Brain, Cells, Cultured, Computer Simulation, Copper, Electron Spin Resonance Spectroscopy, Hydrogen Peroxide, Oxidation-Reduction, Amyloid beta-Peptides, Rats
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