uu.seUppsala University Publications
Change search
CiteExportLink to record
Permanent link

Direct link
Cite
Citation style
  • apa
  • ieee
  • modern-language-association
  • vancouver
  • Other style
More styles
Language
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Other locale
More languages
Output format
  • html
  • text
  • asciidoc
  • rtf
Pathways of Amyloid-β Aggregation Depend on Oligomer Shape
Forschungszentrum Jülich GmbH, Institute of Complex Systems: Structural Biochemistry (ICS-6), Jülich; Heinrich Heine University Düsseldorf, Institute of Theoretical and Computational Chemistry, Düsseldorf.ORCID iD: 0000-0001-7982-3955
Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Cell and Molecular Biology, Structural Biology. Forschungszentrum Jülich GmbH, Institute of Complex Systems: Structural Biochemistry (ICS-6), Jülich.ORCID iD: 0000-0002-2260-8493
Forschungszentrum Jülich GmbH, Institute of Complex Systems: Structural Biochemistry (ICS-6), Jülich; Heinrich Heine University Düsseldorf, Institute of Theoretical and Computational Chemistry, Düsseldorf.ORCID iD: 0000-0002-8734-7765
2018 (English)In: Journal of the American Chemical Society, ISSN 0002-7863, E-ISSN 1520-5126, Vol. 140, no 1, p. 319-327Article in journal (Refereed) Published
Abstract [en]

One of the main research topics related to Alzheimer’s disease is the aggregation of the amyloid-β peptide, which was shown to follow different pathways for the two major alloforms of the peptide, Aβ40 and the more toxic Aβ42. Experimental studies emphasized that oligomers of specific sizes appear in the early aggregation process in different quantities and might be the key toxic agents for each of the two alloforms. We use transition networks derived from all-atom molecular dynamics simulations to show that the oligomers leading to the type of oligomer distributions observed in experiments originate from compact conformations. Extended oligomers, on the other hand, contribute more to the production of larger aggregates thus driving the aggregation process. We further demonstrate that differences in the aggregation pathways of the two Aβ alloforms occur as early as during the dimer stage. The higher solvent-exposure of hydrophobic residues in Aβ42 oligomers contributes to the different aggregation pathways of both alloforms and also to the increased cytotoxicity of Aβ42.

Place, publisher, year, edition, pages
2018. Vol. 140, no 1, p. 319-327
National Category
Biochemistry and Molecular Biology
Identifiers
URN: urn:nbn:se:uu:diva-343382DOI: 10.1021/jacs.7b10343ISI: 000422813300060PubMedID: 29235346OAI: oai:DiVA.org:uu-343382DiVA, id: diva2:1186317
Available from: 2018-02-28 Created: 2018-02-28 Last updated: 2018-03-02Bibliographically approved

Open Access in DiVA

No full text in DiVA

Other links

Publisher's full textPubMed

Authority records BETA

Liao, Qinghua

Search in DiVA

By author/editor
Barz, BogdanLiao, QinghuaStrodel, Birgit
By organisation
Structural Biology
In the same journal
Journal of the American Chemical Society
Biochemistry and Molecular Biology

Search outside of DiVA

GoogleGoogle Scholar

doi
pubmed
urn-nbn

Altmetric score

doi
pubmed
urn-nbn
Total: 24 hits
CiteExportLink to record
Permanent link

Direct link
Cite
Citation style
  • apa
  • ieee
  • modern-language-association
  • vancouver
  • Other style
More styles
Language
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Other locale
More languages
Output format
  • html
  • text
  • asciidoc
  • rtf