Metal ions affect the formation and stability of amyloid β aggregates at multiple length scales

Amyloid β (Aβ) aggregates, which are a hallmark for neurodegenerative disease, are formed through a self-assembly process such as aggregation of Aβ peptide chains. This aggregation process depends on the solvent conditions under which the proteins are aggregated. Nevertheless, the underlying mechani...

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Bibliographic Details
Published inPhysical chemistry chemical physics : PCCP Vol. 20; no. 13; pp. 8951 - 8961
Main Authors Lee, Myeongsang, Kim, Jae In, Na, Sungsoo, Eom, Kilho
Format Journal Article
LanguageEnglish
Published England Royal Society of Chemistry 2018
Subjects
Agglomeration
Aggregates
Amyloid beta-Peptides - chemistry
Amyloid beta-Peptides - metabolism
Copper
Crystallization
Hydrogen bonds
Ions
Ions - chemistry
Metal ions
Metals
Metals - chemistry
Neurological diseases
Oligomers
Protein Stability
Proteins
Self-assembly
Stability
Zinc
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Summary:Amyloid β (Aβ) aggregates, which are a hallmark for neurodegenerative disease, are formed through a self-assembly process such as aggregation of Aβ peptide chains. This aggregation process depends on the solvent conditions under which the proteins are aggregated. Nevertheless, the underlying mechanism of the ionic effect on the formation and stability of amyloid aggregates has not been fully understood. Here, we report how metal ions play a role in the formation and stability of Aβ aggregates at different length scales, i.e. oligomers and fibrils. It is shown that the metal (i.e. zinc or copper) ion increases the stability of Aβ oligomers, whereas the metal ion reduces the stability of Aβ fibrils. In addition, we found that zinc ions are able to more effectively destabilize fibril structures than copper ions. Metal ion-mediated (de)stabilization of Aβ oligomers (or fibrils) is attributed to the critical effect of the metal ion on the β-sheet rich crystalline structure of the amyloid aggregate and the status of hydrogen bonds within the aggregate. Our study sheds light on the role of the metal ion in stabilizing the amyloid oligomers known as a toxic agent (to functional cells), which is consistent with clinical observation that high concentrations of metal ions are found in patients suffering from neurodegenerative diseases.
ISSN:1463-9076
1463-9084
DOI:10.1039/c7cp05072k