Disaggregation Ability of Different Chelating Molecules on Copper Ion-Triggered Amyloid Fibers
Dysfunctional interaction of amyloid-β (Aβ) with excess metal ions is proved to be related to the etiology of Alzheimer’s disease (AD). Using metal-binding compounds to reverse metal-triggered Aβ aggregation has become one of the potential therapies for AD. In this study, the ability of a carboxylic...
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Published in | The journal of physical chemistry. B Vol. 118; no. 31; pp. 9298 - 9305 |
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Main Authors | , , , , |
Format | Journal Article |
Language | English |
Published |
United States
American Chemical Society
07.08.2014
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Subjects | |
Online Access | Get full text |
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Summary: | Dysfunctional interaction of amyloid-β (Aβ) with excess metal ions is proved to be related to the etiology of Alzheimer’s disease (AD). Using metal-binding compounds to reverse metal-triggered Aβ aggregation has become one of the potential therapies for AD. In this study, the ability of a carboxylic acid gemini surfactant (SDUC), a widely used metal chelator (EDTA), and an antifungal drug clioquinol (CQ) in reversing the Cu2+-triggered Aβ(1–40) fibers have been systematically studied by using turbidity essay, BCA essay, atomic force microscopy, transmission electron microscopy, and isothermal titration microcalorimetry. The results show that the binding affinity of Cu2+ with CQ, SDUC, and EDTA is in the order of CQ > EDTA > SDUC, while the disaggregation ability to Cu2+-triggered Aβ(1–40) fibers is in the order of CQ > SDUC > EDTA. Therefore, the disaggregation ability of chelators to the Aβ(1–40) fibers does not only depend on the binding affinity of the chelators with Cu2+. Strong self-assembly ability of SDUC and π–π interaction of the conjugate group of CQ also contributes toward the disaggregation of the Cu2+-triggered Aβ(1–40) fibers and result in the formation of mixed small aggregates. |
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Bibliography: | ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 |
ISSN: | 1520-6106 1520-5207 |
DOI: | 10.1021/jp503282m |