Next Article in Journal
Caudatin Isolated from Cynanchum auriculatum Inhibits Breast Cancer Stem Cell Formation via a GR/YAP Signaling
Next Article in Special Issue
8-Hydroxyquinoline-2-Carboxylic Acid as Possible Molybdophore: A Multi-Technique Approach to Define Its Chemical Speciation, Coordination and Sequestering Ability in Aqueous Solution
Previous Article in Journal
Antioxidant-Based Medicinal Properties of Stingless Bee Products: Recent Progress and Future Directions
Previous Article in Special Issue
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; https://doi.org/10.3390/biom10060924
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
Show Figures

Graphical abstract

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.

Show more citation formats Show less citations formats
Note that from the first issue of 2016, MDPI journals use article numbers instead of page numbers. See further details here.

Article Access Map by Country/Region

1
Search more from Scilit
 
Search
Back to TopTop