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@ARTICLE{Fatafta:902423,
author = {Fatafta, Hebah and Khaled, Mohammed and Owen, Michael C.
and Sayyed-Ahmad, Abdallah and Strodel, Birgit},
title = {{A}myloid-β peptide dimers undergo a random coil to
β-sheet transition in the aqueous phase but not at the
neuronal membrane},
journal = {Proceedings of the National Academy of Sciences of the
United States of America},
volume = {118},
number = {39},
issn = {0027-8424},
address = {Washington, DC},
publisher = {National Acad. of Sciences},
reportid = {FZJ-2021-04245},
pages = {e2106210118 -},
year = {2021},
abstract = {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.},
cin = {IBI-7},
ddc = {500},
cid = {I:(DE-Juel1)IBI-7-20200312},
pnm = {552 - Engineering Cell Function (POF3-552) / 5244 -
Information Processing in Neuronal Networks (POF4-524)},
pid = {G:(DE-HGF)POF3-552 / G:(DE-HGF)POF4-5244},
typ = {PUB:(DE-HGF)16},
pubmed = {pmid:34544868},
UT = {WOS:000708052600007},
doi = {10.1073/pnas.2106210118},
url = {https://juser.fz-juelich.de/record/902423},
}