Journal
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
Volume 113, Issue -, Pages 631-639Publisher
ELSEVIER SCIENCE BV
DOI: 10.1016/j.ijbiomac.2018.02.123
Keywords
Amyloid beta peptide; Zinc ions; Aggregation; Sedimentation velocity; Analytical ultracentrifugation
Funding
- China Scholarship Council (CSC)
- Helmholtz Association through the Helmholtz-Portfolio Topic Technology and Medicine
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The abnormal aggregation of amyloid 3 (A beta) peptides in the brain has been recognized as a central event in Alzheimer's disease (AD). Divalent metal ions such as Zn2+ have been shown to be closely involved in modulating A beta self-association. Although the link between 2n(2+) dyshomeostasis and brain A beta deposition has been established, the effect of Zn2+ on the aggregation of A beta is still incompletely clarified. By combining analytical ultracentrifugation (AUC), circular dichroism (CD) spectroscopy, thiofiavin T (ThT) assay and atomic force microscopy (AFM) imaging, we analyzed the impact of stoichiometric Zn2+ on the aggregation process of A beta 42, the main toxic isoform of A beta species in the brain. A beta 42 aggregates found in the presence of Zn2+ were smaller in size, non-fibrillary and showed less beta-sheet structures than aggregates formed in absence of Zn2+. AUC showed that Zn2+ was capable of retaining monomeric A beta 42 in solution. Zn2+ chelation by EDTA totally reversed the inhibitory effect of Zn2+ on A beta 42 fibrillation. Our results provide further evidence that Zn2+ shifts the self-association of A beta 42 toward a non-fibrillary pathway by interfering with the aggregation process at multiple levels. (C) 2018 Elsevier B.V. All rights reserved.
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