An evaluation of the self-assembly enhancing properties of cell-derived hexameric amyloid-β.
Journal
Scientific reports
ISSN: 2045-2322
Titre abrégé: Sci Rep
Pays: England
ID NLM: 101563288
Informations de publication
Date de publication:
02 06 2021
02 06 2021
Historique:
received:
15
12
2020
accepted:
04
05
2021
entrez:
3
6
2021
pubmed:
4
6
2021
medline:
9
11
2021
Statut:
epublish
Résumé
A key hallmark of Alzheimer's disease is the extracellular deposition of amyloid plaques composed primarily of the amyloidogenic amyloid-β (Aβ) peptide. The Aβ peptide is a product of sequential cleavage of the Amyloid Precursor Protein, the first step of which gives rise to a C-terminal Fragment (C99). Cleavage of C99 by γ-secretase activity releases Aβ of several lengths and the Aβ42 isoform in particular has been identified as being neurotoxic. The misfolding of Aβ leads to subsequent amyloid fibril formation by nucleated polymerisation. This requires an initial and critical nucleus for self-assembly. Here, we identify and characterise the composition and self-assembly properties of cell-derived hexameric Aβ42 and show its assembly enhancing properties which are dependent on the Aβ monomer availability. Identification of nucleating assemblies that contribute to self-assembly in this way may serve as therapeutic targets to prevent the formation of toxic oligomers.
Identifiants
pubmed: 34078941
doi: 10.1038/s41598-021-90680-y
pii: 10.1038/s41598-021-90680-y
pmc: PMC8172837
doi:
Substances chimiques
Amyloid beta-Peptides
0
Biopolymers
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
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