s41598-021-90680-y.pdf (3.72 MB)
An evaluation of the self-assembly enhancing properties of cell-derived hexameric amyloid-ß
journal contribution
posted on 2023-06-10, 00:39 authored by Devkee M Vadukul, Céline Vrancx, Pierre Burguet, Sabrina Contino, Nuria Suelves, Louise SerpellLouise Serpell, Loïc Quinton, Pascal Kienlen-CampardA key hallmark of Alzheimer’s disease is the extracellular deposition of amyloid plaques composed primarily of the amyloidogenic amyloid-ß (Aß) peptide. The Aß 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 ?-secretase activity releases Aß of several lengths and the Aß42 isoform in particular has been identified as being neurotoxic. The misfolding of Aß 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 Aß42 and show its assembly enhancing properties which are dependent on the Aß 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.
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Publication status
- Published
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- Published version
Journal
Scientific ReportsISSN
2045-2322Publisher
Nature ResearchExternal DOI
Issue
1Volume
11Page range
1-17Article number
a11570Event location
EnglandDepartment affiliated with
- Neuroscience Publications
Full text available
- Yes
Peer reviewed?
- Yes
Legacy Posted Date
2021-08-17First Open Access (FOA) Date
2021-08-17First Compliant Deposit (FCD) Date
2021-08-17Usage metrics
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