| Structural insight into the differential effects of omega-3 and omega-6 fatty acids on the production of Abeta peptides and amyloid plaques. | |
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MedLine Citation:
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PMID: 20971855 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Several studies have shown the protective effects of dietary enrichment of various lipids in several late-onset animal models of Alzheimer Disease (AD); however, none of the studies has determined which structure within a lipid determines its detrimental or beneficial effects on AD. High-sensitivity enzyme-linked immunosorbent assay (ELISA) shows that saturated fatty acids (SFAs), upstream omega-3 FAs, and arachidonic acid (AA) resulted in significantly higher secretion of both Aβ 40 and 42 peptides compared with long chain downstream omega-3 and monounsaturated FAs (MUFA). Their distinct detrimental action is believed to be due to a structural template found in their fatty acyl chains that lack SFAs, upstream omega-3 FAs, and AA. Immunoblotting experiments and use of APP-C99-transfected COS-7 cells suggest that FA-driven altered production of Aβ is mediated through γ-secretase cleavage of APP. An early-onset AD transgenic mouse model expressing the double-mutant form of human amyloid precursor protein (APP); Swedish (K670N/M671L) and Indiana (V717F), corroborated in vitro findings by showing lower levels of Aβ and amyloid plaques in the brain, when they were fed a low fat diet enriched in DHA. Our work contributes to the clarification of aspects of structure-activity relationships. |
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Authors:
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Zareen Amtul; Markus Uhrig; Richard F Rozmahel; Konrad Beyreuther |
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Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't Date: 2010-10-22 |
Journal Detail:
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Title: The Journal of biological chemistry Volume: 286 ISSN: 1083-351X ISO Abbreviation: J. Biol. Chem. Publication Date: 2011 Feb |
Date Detail:
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Created Date: 2011-02-21 Completed Date: 2011-04-14 Revised Date: 2012-02-27 |
Medline Journal Info:
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Nlm Unique ID: 2985121R Medline TA: J Biol Chem Country: United States |
Other Details:
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Languages: eng Pagination: 6100-7 Citation Subset: IM |
Affiliation:
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Zentrum für Molekulare Biologie Heidelberg, University of Heidelberg, Heidelberg, Germany. zamtul@uwo.ca |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Alzheimer Disease
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genetics,
metabolism*,
pathology Amyloid / genetics, metabolism* Amyloid Precursor Protein Secretases / genetics, metabolism Amyloid beta-Protein Precursor / biosynthesis*, genetics Animals Brain / metabolism, pathology COS Cells Cercopithecus aethiops Disease Models, Animal Fatty Acids, Omega-3 / metabolism, pharmacology* Fatty Acids, Omega-6 / metabolism, pharmacology* Humans Mice Mice, Mutant Strains Peptides / genetics, metabolism* |
| Grant Support | |
ID/Acronym/Agency:
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MOP49546//Canadian Institutes of Health Research |
| Chemical | |
Reg. No./Substance:
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0/APP protein, human; 0/Amyloid; 0/Amyloid beta-Protein Precursor; 0/Fatty Acids, Omega-3; 0/Fatty Acids, Omega-6; 0/Peptides; EC 3.4.-/Amyloid Precursor Protein Secretases |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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