Skip to main content

Lund University Publications

LUND UNIVERSITY LIBRARIES

A Relationship between the Structures and Neurotoxic Effects of Aβ Oligomers Stabilized by Different Metal Ions

Chia, Sean ; Cataldi, Rodrigo Lessa ; Ruggeri, Francesco Simone ; Limbocker, Ryan ; Condado-Morales, Itzel ; Pisani, Katarina ; Possenti, Andrea ; Linse, Sara LU ; Knowles, Tuomas P.J. and Habchi, Johnny , et al. (2023) In ACS Chemical Neuroscience
Abstract

Oligomeric assemblies of the amyloid β peptide (Aβ) have been investigated for over two decades as possible neurotoxic agents in Alzheimer’s disease. However, due to their heterogeneous and transient nature, it is not yet fully established which of the structural features of these oligomers may generate cellular damage. Here, we study distinct oligomer species formed by Aβ40 (the 40-residue form of Aβ) in the presence of four different metal ions (Al3+, Cu2+, Fe2+, and Zn2+) and show that they differ in their structure and toxicity in human neuroblastoma cells. We then describe a correlation between the size of the oligomers and their neurotoxic activity, which provides a type of... (More)

Oligomeric assemblies of the amyloid β peptide (Aβ) have been investigated for over two decades as possible neurotoxic agents in Alzheimer’s disease. However, due to their heterogeneous and transient nature, it is not yet fully established which of the structural features of these oligomers may generate cellular damage. Here, we study distinct oligomer species formed by Aβ40 (the 40-residue form of Aβ) in the presence of four different metal ions (Al3+, Cu2+, Fe2+, and Zn2+) and show that they differ in their structure and toxicity in human neuroblastoma cells. We then describe a correlation between the size of the oligomers and their neurotoxic activity, which provides a type of structure-toxicity relationship for these Aβ40 oligomer species. These results provide insight into the possible role of metal ions in Alzheimer’s disease by the stabilization of Aβ oligomers.

(Less)
Please use this url to cite or link to this publication:
author
; ; ; ; ; ; ; ; and , et al. (More)
; ; ; ; ; ; ; ; ; ; and (Less)
organization
publishing date
type
Contribution to journal
publication status
epub
subject
keywords
Alzheimer’s disease, amyloid-β peptide, metal ions, protein aggregation, protein misfolding, protein oligomers
in
ACS Chemical Neuroscience
publisher
The American Chemical Society (ACS)
external identifiers
  • pmid:38416693
  • scopus:85186484477
ISSN
1948-7193
DOI
10.1021/acschemneuro.3c00718
language
English
LU publication?
yes
id
a5b58540-3399-4792-a280-a95812d897a3
date added to LUP
2024-03-20 11:48:26
date last changed
2024-04-17 11:17:34
@article{a5b58540-3399-4792-a280-a95812d897a3,
  abstract     = {{<p>Oligomeric assemblies of the amyloid β peptide (Aβ) have been investigated for over two decades as possible neurotoxic agents in Alzheimer’s disease. However, due to their heterogeneous and transient nature, it is not yet fully established which of the structural features of these oligomers may generate cellular damage. Here, we study distinct oligomer species formed by Aβ40 (the 40-residue form of Aβ) in the presence of four different metal ions (Al<sup>3+</sup>, Cu<sup>2+</sup>, Fe<sup>2+</sup>, and Zn<sup>2+</sup>) and show that they differ in their structure and toxicity in human neuroblastoma cells. We then describe a correlation between the size of the oligomers and their neurotoxic activity, which provides a type of structure-toxicity relationship for these Aβ40 oligomer species. These results provide insight into the possible role of metal ions in Alzheimer’s disease by the stabilization of Aβ oligomers.</p>}},
  author       = {{Chia, Sean and Cataldi, Rodrigo Lessa and Ruggeri, Francesco Simone and Limbocker, Ryan and Condado-Morales, Itzel and Pisani, Katarina and Possenti, Andrea and Linse, Sara and Knowles, Tuomas P.J. and Habchi, Johnny and Mannini, Benedetta and Vendruscolo, Michele}},
  issn         = {{1948-7193}},
  keywords     = {{Alzheimer’s disease; amyloid-β peptide; metal ions; protein aggregation; protein misfolding; protein oligomers}},
  language     = {{eng}},
  publisher    = {{The American Chemical Society (ACS)}},
  series       = {{ACS Chemical Neuroscience}},
  title        = {{A Relationship between the Structures and Neurotoxic Effects of Aβ Oligomers Stabilized by Different Metal Ions}},
  url          = {{http://dx.doi.org/10.1021/acschemneuro.3c00718}},
  doi          = {{10.1021/acschemneuro.3c00718}},
  year         = {{2023}},
}