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

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2019
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Abstract
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.
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wallin2019mercurybiomolecules Use this key to autocite in the manuscript while using SciMatic Manuscript Manager or Thesis Manager
Authors Wallin, Cecilia;Friedemann, Merlin;Sholts, Sabrina B;Noormägi, Andra;Svantesson, Teodor;Jarvet, Jüri;Roos, Per M;Palumaa, Peep;Gräslund, Astrid;Wärmländer, Sebastian K T S;
Journal Biomolecules
Year 2019
DOI
E44
URL
Keywords
mercury alzheimer’s disease neurodegeneration amyloid aggregation metal–protein binding eugenol renewable resources thermosets Screening Education stroke sickle cell disease transcranial doppler (tcd) eudragit® s100 hiv sexual transmission tenofovir controlled release chitosan citrate chitosan lactate chitosan tartrate layer-by-layer film mucoadhesive film ph responsive release vaginal preexposure prophylaxis Evaluation behaviour change primary care self-care general practice antibiotic pharmacist

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