TY  - JOUR
AU  - Fatafta, Hebah
AU  - Khaled, Mohammed
AU  - Owen, Michael C.
AU  - Sayyed-Ahmad, Abdallah
AU  - Strodel, Birgit
TI  - Amyloid-β peptide dimers undergo a random coil to β-sheet transition in the aqueous phase but not at the neuronal membrane
JO  - Proceedings of the National Academy of Sciences of the United States of America
VL  - 118
IS  - 39
SN  - 0027-8424
CY  - Washington, DC
PB  - National Acad. of Sciences
M1  - FZJ-2021-04245
SP  - e2106210118 -
PY  - 2021
AB  - 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.
LB  - PUB:(DE-HGF)16
C6  - pmid:34544868
UR  - <Go to ISI:>//WOS:000708052600007
DO  - DOI:10.1073/pnas.2106210118
UR  - https://juser.fz-juelich.de/record/902423
ER  -