Structural insight into the differential effects of omega-3 and omega-6 fatty acids on the production of Aβ peptides and amyloid plaques
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...
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| Main Authors: | , , , |
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| Format: | Article (Journal) |
| Language: | English |
| Published: |
2011
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| In: |
The journal of biological chemistry
Year: 2011, Volume: 286, Issue: 8, Pages: 6100-6107 |
| ISSN: | 1083-351X |
| DOI: | 10.1074/jbc.M110.183608 |
| Online Access: | Verlag, lizenzpflichtig, Volltext: https://doi.org/10.1074/jbc.M110.183608 Verlag, lizenzpflichtig, Volltext: https://www.sciencedirect.com/science/article/pii/S0021925820519856 
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| Author Notes: | Zareen Amtul, Markus Uhrig, Richard F. Rozmahel, Konrad Beyreuther |
| Summary: | 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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| Item Description: | Available online 22 October 2010 Gesehen am 02.03.2022 |
| Physical Description: | Online Resource |
| ISSN: | 1083-351X |
| DOI: | 10.1074/jbc.M110.183608 |