Journal
ARCHIVES OF BIOCHEMISTRY AND BIOPHYSICS
Volume 663, Issue -, Pages 34-43Publisher
ELSEVIER SCIENCE INC
DOI: 10.1016/j.abb.2018.12.027
Keywords
Polyunsaturated fatty acids; Amyloid-beta; Aggregation kinetics; Alzheimer's disease; Transmission electron microscopy; Molecular docking
Categories
Funding
- NSERC-Discovery [RGPIN: 03830-2014]
- Early Researcher Award (ERA), Ministry of Research and Innovation, Government of Ontario
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Polyunsaturated fatty acids (PUFAs) are reported to exert beneficial effects in Alzheimer's disease. Some PUFAs are known to reduce amyloid-beta (A beta) toxicity by promoting its degradation and clearance. Studies on the direct interactions of PUFAs with A beta peptides are limited and contradictory. In this study, we report the interactions of fatty acids docosahexaenoic acid (DHA), eicosatetraenoic acid (EPA), alpha-linolenic acid (ALA), arachidonic acid (ARA), linoleic acid (LNA) and oleic acid (OA) with A beta 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 A beta 40 and A beta 42 fibrillogenesis (similar to 16-84% inhibition). OA and DHA were identified as excellent inhibitors of A beta 40 or A beta 42 fibrillogenesis respectively (similar to 84% and 81% inhibition at 25 mu M). Molecular docking studies conducted, using the dimer and oligomer models of A beta 40 peptide, suggest that these fatty acids interact in the aggregation prone Phe19-Ala21 and the beta-turn region (Asp23-Lys28) whereas a similar study with A beta 42 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 A beta 40 and A beta 42 peptides. These studies will have implications in developing potential therapeutics for Alzheimer's disease.
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