Omega‑3 Fatty Acids Regulate the Interaction
of the Alzheimer’s Aβ(25–35) Peptide with Lipid
Membranes
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Abstract
Polyunsaturated
omega-3 fatty acids are increasingly proposed as
dietary supplements able to reduce the risk of development or progression
of the Alzheimer’s disease (AD). To date, the molecular mechanism
through which these lipids act has not been yet univocally identified.
In this work, we investigate whether omega-3 fatty acids could interfere
with the fate of the Alzheimer-related amyloid peptide by tuning the
microstructural and dynamical properties of the neuronal membrane.
To this aim, the influence of the omega-3 lipid, 1,2-didocosahexaenoyl-<i>sn</i>-glycero-3-phosphocholine [22:6(<i><i>cis</i></i>)PC] on the biophysical properties of lipid bilayers, and
on their interaction with the amyloid peptide fragment Aβ(25–35)
has been investigated by Electron Spin Resonance (ESR), using spin-labeled
phospholipids. The results show that the peptide selectively interacts
with bilayers enriched in cholesterol (Chol) and sphingomyelin (SM).
[22:6(<i><i>cis</i></i>)PC] enhances the Aβ(25–35)/membrane
interaction, favoring a deeper internalization of the peptide among
the lipid acyl chains and, consequently, hindering its pathogenic
self-aggregation