期刊
ARCHIVES OF BIOCHEMISTRY AND BIOPHYSICS
卷 663, 期 -, 页码 34-43出版社
ELSEVIER SCIENCE INC
DOI: 10.1016/j.abb.2018.12.027
关键词
Polyunsaturated fatty acids; Amyloid-beta; Aggregation kinetics; Alzheimer's disease; Transmission electron microscopy; Molecular docking
资金
- NSERC-Discovery [RGPIN: 03830-2014]
- Early Researcher Award (ERA), Ministry of Research and Innovation, Government of Ontario
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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