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Open AccessArticle

Mercury and Alzheimer’s Disease: Hg(II) Ions Display Specific Binding to the Amyloid-β Peptide and Hinder Its Fibrillization

1
Department of Biochemistry and Biophysics, Stockholm University, 10691 Stockholm, Sweden
2
Department of Chemistry and Biotechnology, Tallinn University of Technology, 19086 Tallinn, Estonia
3
Department of Anthropology, National Museum of Natural History, Smithsonian Institution, Washington, DC 20560, USA
4
The National Institute of Chemical Physics and Biophysics, 12618 Tallinn, Estonia
5
Institute of Environmental Medicine, Karolinska Institutet, 16765 Stockholm, Sweden
6
Department of Clinical Physiology, Capio St. Göran Hospital, 11219 Stockholm, Sweden
*
Author to whom correspondence should be addressed.
Biomolecules 2020, 10(1), 44; https://doi.org/10.3390/biom10010044
Received: 22 November 2019 / Revised: 20 December 2019 / Accepted: 20 December 2019 / Published: 27 December 2019
(This article belongs to the Special Issue Toxic and Essential Metals in Human Health and Disease)
Brains and blood of Alzheimer’s disease (AD) patients have shown elevated mercury concentrations, but potential involvement of mercury exposure in AD pathogenesis has not been studied at the molecular level. The pathological hallmark of AD brains is deposition of amyloid plaques, consisting mainly of amyloid-β (Aβ) peptides aggregated into amyloid fibrils. Aβ peptide fibrillization is known to be modulated by metal ions such as Cu(II) and Zn(II). Here, we study in vitro the interactions between Aβ peptides and Hg(II) ions by multiple biophysical techniques. Fluorescence spectroscopy and atomic force microscopy (AFM) show that Hg(II) ions have a concentration-dependent inhibiting effect on Aβ fibrillization: at a 1:1 Aβ·Hg(II) ratio only non-fibrillar Aβ aggregates are formed. NMR spectroscopy shows that Hg(II) ions interact with the N-terminal region of Aβ(1–40) with a micromolar affinity, likely via a binding mode similar to that for Cu(II) and Zn(II) ions, i.e., mainly via the histidine residues His6, His13, and His14. Thus, together with Cu(II), Fe(II), Mn(II), Pb(IV), and Zn(II) ions, Hg(II) belongs to a family of metal ions that display residue-specific binding interactions with Aβ peptides and modulate their aggregation processes. View Full-Text
Keywords: mercury; Alzheimer’s disease; amyloid aggregation; metal–protein binding; neurodegeneration mercury; Alzheimer’s disease; amyloid aggregation; metal–protein binding; neurodegeneration
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Wallin, C.; Friedemann, M.; Sholts, S.B.; Noormägi, A.; Svantesson, T.; Jarvet, J.; Roos, P.M.; Palumaa, P.; Gräslund, A.; Wärmländer, S.K.T.S. Mercury and Alzheimer’s Disease: Hg(II) Ions Display Specific Binding to the Amyloid-β Peptide and Hinder Its Fibrillization. Biomolecules 2020, 10, 44.

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