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Agricultural Use of Copper and Its Link to Alzheimer’s Disease
Open AccessArticle

Redox-Dependent Copper Ion Modulation of Amyloid-β (1-42) Aggregation In Vitro

Department of Biology and Biological Engineering, Chalmers University of Technology, 412 96 Gothenburg, Sweden
Author to whom correspondence should be addressed.
Biomolecules 2020, 10(6), 924;
Received: 15 May 2020 / Revised: 12 June 2020 / Accepted: 16 June 2020 / Published: 18 June 2020
(This article belongs to the Special Issue Toxic and Essential Metals in Human Health and Disease)
Plaque deposits composed of amyloid-β (Aβ) fibrils are pathological hallmarks of Alzheimer’s disease (AD). Although copper ion dyshomeostasis is apparent in AD brains and copper ions are found co-deposited with Aβ peptides in patients’ plaques, the molecular effects of copper ion interactions and redox-state dependence on Aβ aggregation remain elusive. By combining biophysical and theoretical approaches, we here show that Cu2+ (oxidized) and Cu+ (reduced) ions have opposite effects on the assembly kinetics of recombinant Aβ(1-42) into amyloid fibrils in vitro. Cu2+ inhibits both the unseeded and seeded aggregation of Aβ(1-42) at pH 8.0. Using mathematical models to fit the kinetic data, we find that Cu2+ prevents fibril elongation. The Cu2+-mediated inhibition of Aβ aggregation shows the largest effect around pH 6.0 but is lost at pH 5.0, which corresponds to the pH in lysosomes. In contrast to Cu2+, Cu+ ion binding mildly catalyzes the Aβ(1-42) aggregation via a mechanism that accelerates primary nucleation, possibly via the formation of Cu+-bridged Aβ(1-42) dimers. Taken together, our study emphasizes redox-dependent copper ion effects on Aβ(1-42) aggregation and thereby provides further knowledge of putative copper-dependent mechanisms resulting in AD. View Full-Text
Keywords: amyloid; amyloid-β; copper; aggregation; kinetics; inhibition; Alzheimer’s disease amyloid; amyloid-β; copper; aggregation; kinetics; inhibition; Alzheimer’s disease
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MDPI and ACS Style

Sasanian, N.; Bernson, D.; Horvath, I.; Wittung-Stafshede, P.; Esbjörner, E.K. Redox-Dependent Copper Ion Modulation of Amyloid-β (1-42) Aggregation In Vitro. Biomolecules 2020, 10, 924.

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