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[PMID]: | 28634213 |
[Au] Autor: | Olivera-Perez HM; Lam L; Dang J; Jiang W; Rodriguez F; Rigali E; Weitzman S; Porter V; Rubbi L; Morselli M; Pellegrini M; Fiala M |
[Ad] Endereço: | Department of Cell, Molecular, and Developmental Biology, UCLA Life Sciences, University of California, Los Angeles, Los Angeles, California, USA. |
[Ti] Título: | Omega-3 fatty acids increase the unfolded protein response and improve amyloid-ß phagocytosis by macrophages of patients with mild cognitive impairment. |
[So] Source: | FASEB J;31(10):4359-4369, 2017 Oct. | [Is] ISSN: | 1530-6860 |
[Cp] País de publicação: | United States |
[La] Idioma: | eng |
[Ab] Resumo: | Macrophages (MÏ•s) of patients with Alzheimer's disease and mild cognitive impairment (MCI) are defective in amyloid-ß (Aß) phagocytosis and have low resistance to apoptosis by Aß. Omega-3 fatty acids (ω-3s) and and the ω-3 mediator, resolvin D1, increase Aß phagocytosis by MÏ•s of patients with MCI. We have investigated the unfolded protein response (UPR) to endoplasmic reticulum (ER) stress by MÏ•s in a longitudinal study of fish-derived, ω-3-supplemented patients with MCI. Patients in the apolipoprotein E (ApoE)e3/e3 subgroup over time exhibited an increase of protein kinase RNA-like ER kinase (PERK) expression, Aß phagocytosis, intermediate M1-M2 MÏ• type, and a Mini-Mental State Examination (MMSE) rate of change of +1.8 points per year, whereas patients in the ApoEe3/e4 subgroup showed individually divergent results with an MMSE rate of change of -3.2 points per year. treatment of MÏ•s by fish-derived ω-3 emulsion increased Aß phagocytosis, PERK expression, and UPR RNA signature, and decreased ER stress signature. Augmented genes in the UPR signature included chaperones, lectins, foldases, and N-linked glycosylation enzymes. In summary, fish-derived ω-3s increase cytoprotective genes and decrease proapoptotic genes, improve immune clearance of Aß, and are associated with an improved MMSE rate of change in ApoEe3/e3 ApoEe3/e4 patients.-Olivera-Perez, H. M., Lam, L., Dang, J., Jiang, W., Rodriguez, F., Rigali, E., Weitzman, S., Porter, V., Rubbi, L., Morselli, M., Pellegrini, M., Fiala, M. Omega-3 fatty acids increase the unfolded protein response and improve amyloid-ß phagocytosis by macrophages of patients with mild cognitive impairment. |
[Mh] Termos MeSH primário: |
Peptídeos beta-Amiloides/metabolismo Disfunção Cognitiva/metabolismo Estresse do Retículo Endoplasmático/efeitos dos fármacos Ácidos Graxos Ômega-3/farmacologia Macrófagos/efeitos dos fármacos Fragmentos de Peptídeos/metabolismo Fagocitose/efeitos dos fármacos
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[Mh] Termos MeSH secundário: |
Doença de Alzheimer/genética Doença de Alzheimer/metabolismo Proteínas Amiloidogênicas/metabolismo Apoptose/efeitos dos fármacos Apoptose/fisiologia Ácidos Graxos Ômega-3/metabolismo Seres Humanos Macrófagos/metabolismo Desdobramento de Proteína
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[Pt] Tipo de publicação: | JOURNAL ARTICLE |
[Nm] Nome de substância:
| 0 (Amyloid beta-Peptides); 0 (Amyloidogenic Proteins); 0 (Fatty Acids, Omega-3); 0 (Peptide Fragments); 0 (amyloid beta-protein (1-42)) |
[Em] Mês de entrada: | 1710 |
[Cu] Atualização por classe: | 171019 |
[Lr] Data última revisão:
| 171019 |
[Sb] Subgrupo de revista: | IM |
[Da] Data de entrada para processamento: | 170622 |
[St] Status: | MEDLINE |
[do] DOI: | 10.1096/fj.201700290R |
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