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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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Mutter, S. T., Turner, M., Deeth, R. J., & Platts, J. A. (2019) · Heliyon · doi:10.1016/j.heliyon.2019.e03071 · Cited by 10
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Barry, S. D., Rickard, G. A., Pushie, M. J., & Rauk, A. (2009) · Canadian Journal of Chemistry · doi:10.1139/v09-034 · Cited by 10
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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
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
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