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Interactions of polyunsaturated fatty acids with amyloid peptides Aβ40 and Aβ42.

Abstract：

:Polyunsaturated fatty acids (PUFAs) are reported to exert beneficial effects in Alzheimer's disease. Some PUFAs are known to reduce amyloid-beta (Aβ) toxicity by promoting its degradation and clearance. Studies on the direct interactions of PUFAs with Aβ peptides are limited and contradictory. In this study, we report the interactions of fatty acids docosahexaenoic acid (DHA), eicosatetraenoic acid (EPA), α-linolenic acid (ALA), arachidonic acid (ARA), linoleic acid (LNA) and oleic acid (OA) with Aβ peptides by carrying out fluorescence based aggregation kinetic experiments, transmission electron microscopy and molecular docking studies. Our investigations demonstrate that all the fatty acids tested exhibit anti-aggregation properties by preventing both Aβ40 and Aβ42 fibrillogenesis (∼16-84% inhibition). OA and DHA were identified as excellent inhibitors of Aβ40 or Aβ42 fibrillogenesis respectively (∼84% and 81% inhibition at 25 μM). Molecular docking studies conducted, using the dimer and oligomer models of Aβ40 peptide, suggest that these fatty acids interact in the aggregation prone Phe19-Ala21 and the β-turn region (Asp23-Lys28) whereas a similar study with Aβ42 dimer and oligomer models, indicate that the fatty acids were oriented in a hydrophobic region (Gln15, Leu16, Leu17 and Leu34). These results, suggest that DHA, EPA, ALA, ARA, LNA and OA are capable of directly interacting with both Aβ40 and Aβ42 peptides. These studies will have implications in developing potential therapeutics for Alzheimer's disease.

journal_name

Arch Biochem Biophys

journal_title

Archives of biochemistry and biophysics

authors

El Shatshat A,Pham AT,Rao PPN

doi

10.1016/j.abb.2018.12.027

subject

Has Abstract

pub_date

2019-03-15 00:00:00

pages

34-43

eissn

0003-9861

issn

1096-0384

pii

S0003-9861(18)30657-X

journal_volume

663

pub_type

杂志文章

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