%0 Journal Article
%A Fatafta, Hebah
%A Khaled, Mohammed
%A Owen, Michael C.
%A Sayyed-Ahmad, Abdallah
%A Strodel, Birgit
%T Amyloid-β peptide dimers undergo a random coil to β-sheet transition in the aqueous phase but not at the neuronal membrane
%J Proceedings of the National Academy of Sciences of the United States of America
%V 118
%N 39
%@ 0027-8424
%C Washington, DC
%I National Acad. of Sciences
%M FZJ-2021-04245
%P e2106210118 -
%D 2021
%X Mounting evidence suggests that the neuronal cell membrane is the main site of oligomer-mediated neuronal toxicity of amyloid-β peptides in Alzheimer’s disease. To gain a detailed understanding of the mutual interference of amyloid-β oligomers and the neuronal membrane, we carried out microseconds of all-atom molecular dynamics (MD) simulations on the dimerization of amyloid-β (Aβ)42 in the aqueous phase and in the presence of a lipid bilayer mimicking the in vivo composition of neuronal membranes. The dimerization in solution is characterized by a random coil to β-sheet transition that seems on pathway to amyloid aggregation, while the interactions with the neuronal membrane decrease the order of the Aβ42 dimer by attenuating its propensity to form a β-sheet structure. The main lipid interaction partners of Aβ42 are the surface-exposed sugar groups of the gangliosides GM1. As the neurotoxic activity of amyloid oligomers increases with oligomer order, these results suggest that GM1 is neuroprotective against Aβ-mediated toxicity.
%F PUB:(DE-HGF)16
%9 Journal Article
%$ pmid:34544868
%U <Go to ISI:>//WOS:000708052600007
%R 10.1073/pnas.2106210118
%U https://juser.fz-juelich.de/record/902423