This title appears in the Scientific Report :
2021
Please use the identifier:
http://hdl.handle.net/2128/30321 in citations.
Please use the identifier: http://dx.doi.org/10.1073/pnas.2106210118 in citations.
Amyloid-β peptide dimers undergo a random coil to β-sheet transition in the aqueous phase but not at the neuronal membrane
Amyloid-β peptide dimers undergo a random coil to β-sheet transition in the aqueous phase but not at the neuronal membrane
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 o...
Saved in:
Personal Name(s): | Fatafta, Hebah |
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Khaled, Mohammed / Owen, Michael C. / Sayyed-Ahmad, Abdallah / Strodel, Birgit (Corresponding author) | |
Contributing Institute: |
Strukturbiochemie; IBI-7 |
Published in: | Proceedings of the National Academy of Sciences of the United States of America, 118 (2021) 39, S. e2106210118 - |
Imprint: |
Washington, DC
National Acad. of Sciences
2021
|
PubMed ID: |
34544868 |
DOI: |
10.1073/pnas.2106210118 |
Document Type: |
Journal Article |
Research Program: |
Information Processing in Neuronal Networks Engineering Cell Function |
Link: |
OpenAccess |
Publikationsportal JuSER |
Please use the identifier: http://dx.doi.org/10.1073/pnas.2106210118 in citations.
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. |