Mercury and Alzheimer’s Disease: Hg(II) Ions Display Specific Binding to the Amyloid-β Peptide and Hinder Its Fibrillization
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, consistin...
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| Format: | Article |
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MDPI AG
2019-12-01
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| Series: | Biomolecules |
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| Online Access: | https://www.mdpi.com/2218-273X/10/1/44 |
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| author | Cecilia Wallin Merlin Friedemann Sabrina B. Sholts Andra Noormägi Teodor Svantesson Jüri Jarvet Per M. Roos Peep Palumaa Astrid Gräslund Sebastian K. T. S. Wärmländer |
| author_facet | Cecilia Wallin Merlin Friedemann Sabrina B. Sholts Andra Noormägi Teodor Svantesson Jüri Jarvet Per M. Roos Peep Palumaa Astrid Gräslund Sebastian K. T. S. Wärmländer |
| author_sort | Cecilia Wallin |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-12-20T21:35:16Z |
| format | Article |
| id | doaj.art-f1e9234820bb44aa8b827199b8521424 |
| institution | Directory Open Access Journal |
| issn | 2218-273X |
| language | English |
| last_indexed | 2024-12-20T21:35:16Z |
| publishDate | 2019-12-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Biomolecules |
| spelling | doaj.art-f1e9234820bb44aa8b827199b85214242022-12-21T19:25:58ZengMDPI AGBiomolecules2218-273X2019-12-011014410.3390/biom10010044biom10010044Mercury and Alzheimer’s Disease: Hg(II) Ions Display Specific Binding to the Amyloid-β Peptide and Hinder Its FibrillizationCecilia Wallin0Merlin Friedemann1Sabrina B. Sholts2Andra Noormägi3Teodor Svantesson4Jüri Jarvet5Per M. Roos6Peep Palumaa7Astrid Gräslund8Sebastian K. T. S. Wärmländer9Department of Biochemistry and Biophysics, Stockholm University, 10691 Stockholm, SwedenDepartment of Chemistry and Biotechnology, Tallinn University of Technology, 19086 Tallinn, EstoniaDepartment of Anthropology, National Museum of Natural History, Smithsonian Institution, Washington, DC 20560, USADepartment of Chemistry and Biotechnology, Tallinn University of Technology, 19086 Tallinn, EstoniaDepartment of Biochemistry and Biophysics, Stockholm University, 10691 Stockholm, SwedenDepartment of Biochemistry and Biophysics, Stockholm University, 10691 Stockholm, SwedenInstitute of Environmental Medicine, Karolinska Institutet, 16765 Stockholm, SwedenDepartment of Chemistry and Biotechnology, Tallinn University of Technology, 19086 Tallinn, EstoniaDepartment of Biochemistry and Biophysics, Stockholm University, 10691 Stockholm, SwedenDepartment of Biochemistry and Biophysics, Stockholm University, 10691 Stockholm, SwedenBrains 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.https://www.mdpi.com/2218-273X/10/1/44mercuryalzheimer’s diseaseamyloid aggregationmetal–protein bindingneurodegeneration |
| spellingShingle | Cecilia Wallin Merlin Friedemann Sabrina B. Sholts Andra Noormägi Teodor Svantesson Jüri Jarvet Per M. Roos Peep Palumaa Astrid Gräslund Sebastian K. T. S. Wärmländer Mercury and Alzheimer’s Disease: Hg(II) Ions Display Specific Binding to the Amyloid-β Peptide and Hinder Its Fibrillization Biomolecules mercury alzheimer’s disease amyloid aggregation metal–protein binding neurodegeneration |
| title | Mercury and Alzheimer’s Disease: Hg(II) Ions Display Specific Binding to the Amyloid-β Peptide and Hinder Its Fibrillization |
| title_full | Mercury and Alzheimer’s Disease: Hg(II) Ions Display Specific Binding to the Amyloid-β Peptide and Hinder Its Fibrillization |
| title_fullStr | Mercury and Alzheimer’s Disease: Hg(II) Ions Display Specific Binding to the Amyloid-β Peptide and Hinder Its Fibrillization |
| title_full_unstemmed | Mercury and Alzheimer’s Disease: Hg(II) Ions Display Specific Binding to the Amyloid-β Peptide and Hinder Its Fibrillization |
| title_short | Mercury and Alzheimer’s Disease: Hg(II) Ions Display Specific Binding to the Amyloid-β Peptide and Hinder Its Fibrillization |
| title_sort | mercury and alzheimer s disease hg ii ions display specific binding to the amyloid β peptide and hinder its fibrillization |
| topic | mercury alzheimer’s disease amyloid aggregation metal–protein binding neurodegeneration |
| url | https://www.mdpi.com/2218-273X/10/1/44 |
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