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Characterization of Mn(II) ion binding to the amyloid-β peptide in Alzheimer's disease

Wallin, Cecilia ; Kulkarni, Yashraj S ; Abelein, Axel ; Jarvet, Jüri ; Liao, Qinghua ; Strodel, Birgit ; Olsson, Lisa ; Luo, Jinghui ; Abrahams, Jan Pieter and Sholts, Sabrina B , et al. (2016) In Journal of Trace Elements in Medicine and Biology 38. p.183-193
Abstract

Growing evidence links neurodegenerative diseases to metal exposure. Aberrant metal ion concentrations have been noted in Alzheimer's disease (AD) brains, yet the role of metals in AD pathogenesis remains unresolved. A major factor in AD pathogenesis is considered to be aggregation of and amyloid formation by amyloid-β (Aβ) peptides. Previous studies have shown that Aβ displays specific binding to Cu(II) and Zn(II) ions, and such binding has been shown to modulate Aβ aggregation. Here, we use nuclear magnetic resonance (NMR) spectroscopy to show that Mn(II) ions also bind to the N-terminal part of the Aβ(1-40) peptide, with a weak binding affinity in the milli- to micromolar range. Circular dichroism (CD) spectroscopy, solid state... (More)

Growing evidence links neurodegenerative diseases to metal exposure. Aberrant metal ion concentrations have been noted in Alzheimer's disease (AD) brains, yet the role of metals in AD pathogenesis remains unresolved. A major factor in AD pathogenesis is considered to be aggregation of and amyloid formation by amyloid-β (Aβ) peptides. Previous studies have shown that Aβ displays specific binding to Cu(II) and Zn(II) ions, and such binding has been shown to modulate Aβ aggregation. Here, we use nuclear magnetic resonance (NMR) spectroscopy to show that Mn(II) ions also bind to the N-terminal part of the Aβ(1-40) peptide, with a weak binding affinity in the milli- to micromolar range. Circular dichroism (CD) spectroscopy, solid state atomic force microscopy (AFM), fluorescence spectroscopy, and molecular modeling suggest that the weak binding of Mn(II) to Aβ may not have a large effect on the peptide's aggregation into amyloid fibrils. However, identification of an additional metal ion displaying Aβ binding reveals more complex AD metal chemistry than has been previously considered in the literature.

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publishing date
type
Contribution to journal
publication status
published
keywords
Alzheimer Disease/metabolism, Amyloid beta-Peptides/chemistry, Binding Sites, Humans, Ions/chemistry, Manganese/chemistry
in
Journal of Trace Elements in Medicine and Biology
volume
38
pages
11 pages
publisher
Elsevier
external identifiers
  • scopus:84964370109
  • pmid:27085215
ISSN
1878-3252
DOI
10.1016/j.jtemb.2016.03.009
language
English
LU publication?
no
additional info
Copyright © 2016 Elsevier GmbH. All rights reserved.
id
1c4a3c24-b136-4261-b94a-1c243cc73efc
date added to LUP
2025-01-11 21:30:41
date last changed
2025-04-20 11:51:25
@article{1c4a3c24-b136-4261-b94a-1c243cc73efc,
  abstract     = {{<p>Growing evidence links neurodegenerative diseases to metal exposure. Aberrant metal ion concentrations have been noted in Alzheimer's disease (AD) brains, yet the role of metals in AD pathogenesis remains unresolved. A major factor in AD pathogenesis is considered to be aggregation of and amyloid formation by amyloid-β (Aβ) peptides. Previous studies have shown that Aβ displays specific binding to Cu(II) and Zn(II) ions, and such binding has been shown to modulate Aβ aggregation. Here, we use nuclear magnetic resonance (NMR) spectroscopy to show that Mn(II) ions also bind to the N-terminal part of the Aβ(1-40) peptide, with a weak binding affinity in the milli- to micromolar range. Circular dichroism (CD) spectroscopy, solid state atomic force microscopy (AFM), fluorescence spectroscopy, and molecular modeling suggest that the weak binding of Mn(II) to Aβ may not have a large effect on the peptide's aggregation into amyloid fibrils. However, identification of an additional metal ion displaying Aβ binding reveals more complex AD metal chemistry than has been previously considered in the literature.</p>}},
  author       = {{Wallin, Cecilia and Kulkarni, Yashraj S and Abelein, Axel and Jarvet, Jüri and Liao, Qinghua and Strodel, Birgit and Olsson, Lisa and Luo, Jinghui and Abrahams, Jan Pieter and Sholts, Sabrina B and Roos, Per M and Kamerlin, Shina C L and Gräslund, Astrid and Wärmländer, Sebastian K T S}},
  issn         = {{1878-3252}},
  keywords     = {{Alzheimer Disease/metabolism; Amyloid beta-Peptides/chemistry; Binding Sites; Humans; Ions/chemistry; Manganese/chemistry}},
  language     = {{eng}},
  pages        = {{183--193}},
  publisher    = {{Elsevier}},
  series       = {{Journal of Trace Elements in Medicine and Biology}},
  title        = {{Characterization of Mn(II) ion binding to the amyloid-β peptide in Alzheimer's disease}},
  url          = {{http://dx.doi.org/10.1016/j.jtemb.2016.03.009}},
  doi          = {{10.1016/j.jtemb.2016.03.009}},
  volume       = {{38}},
  year         = {{2016}},
}