| Substoichiometric levels of Cu2+ ions accelerate the kinetics of fiber formation and promote cell toxicity of amyloid-{beta} from Alzheimer disease. | |
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MedLine Citation:
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PMID: 20974842 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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A role for Cu(2+) ions in Alzheimer disease is often disputed, as it is believed that Cu(2+) ions only promote nontoxic amorphous aggregates of amyloid-β (Aβ). In contrast with currently held opinion, we show that the presence of substoichiometric levels of Cu(2+) ions in fact doubles the rate of production of amyloid fibers, accelerating both the nucleation and elongation of fiber formation. We suggest that binding of Cu(2+) ions at a physiological pH causes Aβ to approach its isoelectric point, thus inducing self-association and fiber formation. We further show that Cu(2+) ions bound to Aβ are consistently more toxic to neuronal cells than Aβ in the absence of Cu(2+) ions, whereas Cu(2+) ions in the absence of Aβ are not cytotoxic. The degree of Cu-Aβ cytotoxicity correlates with the levels of Cu(2+) ions that accelerate fiber formation. We note the effect appears to be specific for Cu(2+) ions as Zn(2+) ions inhibit the formation of fibers. An active role for Cu(2+) ions in accelerating fiber formation and promoting cell death suggests impaired copper homeostasis may be a risk factor in Alzheimer disease. |
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Authors:
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Claire J Sarell; Shane R Wilkinson; John H Viles |
Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't Date: 2010-10-25 |
Journal Detail:
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Title: The Journal of biological chemistry Volume: 285 ISSN: 1083-351X ISO Abbreviation: J. Biol. Chem. Publication Date: 2010 Dec |
Date Detail:
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Created Date: 2010-12-27 Completed Date: 2011-02-09 Revised Date: 2012-01-02 |
Medline Journal Info:
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Nlm Unique ID: 2985121R Medline TA: J Biol Chem Country: United States |
Other Details:
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Languages: eng Pagination: 41533-40 Citation Subset: IM |
Affiliation:
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School of Biological and Chemical Sciences, Queen Mary University of London, Mile End Road, London E1 4NS, United Kingdom. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Alzheimer Disease
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metabolism* Amyloid beta-Peptides / chemistry* Animals Biophysics / methods Cell Survival Copper / chemistry* Hydrogen-Ion Concentration Ions Isoelectric Point Kinetics Microscopy, Electron, Transmission / methods Neurons / metabolism PC12 Cells Protein Folding Rats Zinc / chemistry |
| Grant Support | |
ID/Acronym/Agency:
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BBD0050271//Biotechnology and Biological Sciences Research Council |
| Chemical | |
Reg. No./Substance:
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0/Amyloid beta-Peptides; 0/Ions; 7440-50-8/Copper; 7440-66-6/Zinc |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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