TY  - JOUR
AU  - Hasecke, Filip
AU  - Niyangoda, Chamani
AU  - Borjas, Gustavo
AU  - Pan, Jianjun
AU  - Matthews, Garrett
AU  - Muschol, Martin
AU  - Hoyer, Wolfgang
TI  - Protofibril‐Fibril Interactions Inhibit Amyloid Fibril Assembly by Obstructing Secondary Nucleation
JO  - Angewandte Chemie / International edition
VL  - 60
IS  - 6
SN  - 1521-3773
CY  - Weinheim
PB  - Wiley-VCH
M1  - FZJ-2020-04792
SP  - 3016-3021
PY  - 2021
AB  - 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.
LB  - PUB:(DE-HGF)16
C6  - 33095508
UR  - <Go to ISI:>//WOS:000598234800001
DO  - DOI:10.1002/anie.202010098
UR  - https://juser.fz-juelich.de/record/888243
ER  -