Journal Article

FZJ-2020-04792

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png Protofibril‐Fibril Interactions Inhibit Amyloid Fibril Assembly by Obstructing Secondary Nucleation

Hasecke, F. ; Niyangoda, C. ; Borjas, G. ; Pan, J. ; Matthews, G. ; Muschol, M. (Corresponding author) ; Hoyer, W. (Corresponding author)FZJ*

2021
Wiley-VCH Weinheim

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Please use a persistent id in citations: http://hdl.handle.net/2128/27163  doi:10.1002/anie.202010098

Abstract: Amyloid-b peptides (Ab) assemble into both rigidamyloid fibrils and metastable oligomers termed AbO orprotofibrils. In Alzheimers disease, Ab fibrils constitute thecore of senile plaques, but Ab protofibrils may represent themain toxic species. Ab protofibrils accumulate at the exterior ofsenile plaques, yet the protofibril–fibril interplay is not wellunderstood. Applying chemical kinetics and atomic forcemicroscopy to the assembly of Ab and lysozyme, protofibrilsare observed to bind to the lateral surfaces of amyloid fibrils.When utilizing Ab variants with different critical oligomerconcentrations, the interaction inhibits the autocatalytic proliferationof amyloid fibrils by secondary nucleation on thefibril surface. Thus, metastable oligomers antagonize theirreplacement by amyloid fibrils both by competing for monomersand blocking secondary nucleation sites. The protofibril—fibril interaction governs their temporal evolution andpotential to exert specific toxic activities.

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Contributing Institute(s):

1. Strukturbiochemie (IBI-7)

Research Program(s):

1. 5244 - Information Processing in Neuronal Networks (POF4-524) (POF4-524)
2. BETACONTROL - Control of amyloid formation via beta-hairpin molecular recognition features (726368) (726368)

Appears in the scientific report 2021

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Database coverage:
; ; ; Chemical Reactions ; Clarivate Analytics Master Journal List ; Current Contents - Life Sciences ; Current Contents - Physical, Chemical and Earth Sciences ; DEAL Wiley ; Ebsco Academic Search ; Essential Science Indicators ; IF >= 10 ; Index Chemicus ; JCR ; Nationallizenz ; SCOPUS ; Science Citation Index Expanded ; Web of Science Core Collection

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