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Omega-3 fatty acids increase the unfolded protein response and improve amyloid-ß phagocytosis by macrophages of patients with mild cognitive impairment.
Olivera-Perez, Henry M; Lam, Larry; Dang, Johnny; Jiang, Weilan; Rodriguez, Fabian; Rigali, Elizabeth; Weitzman, Sarah; Porter, Verna; Rubbi, Liudmilla; Morselli, Marco; Pellegrini, Matteo; Fiala, Milan.
Afiliação
  • Olivera-Perez HM; Department of Cell, Molecular, and Developmental Biology, UCLA Life Sciences, University of California, Los Angeles, Los Angeles, California, USA.
  • Lam L; Department of Cell, Molecular, and Developmental Biology, UCLA Life Sciences, University of California, Los Angeles, Los Angeles, California, USA.
  • Dang J; Department of Cell, Molecular, and Developmental Biology, UCLA Life Sciences, University of California, Los Angeles, Los Angeles, California, USA.
  • Jiang W; Department of Cell, Molecular, and Developmental Biology, UCLA Life Sciences, University of California, Los Angeles, Los Angeles, California, USA.
  • Rodriguez F; Department of Cell, Molecular, and Developmental Biology, UCLA Life Sciences, University of California, Los Angeles, Los Angeles, California, USA.
  • Rigali E; Department of Cell, Molecular, and Developmental Biology, UCLA Life Sciences, University of California, Los Angeles, Los Angeles, California, USA.
  • Weitzman S; Department of Cell, Molecular, and Developmental Biology, UCLA Life Sciences, University of California, Los Angeles, Los Angeles, California, USA.
  • Porter V; Department of Neurology, UCLA School of Medicine, University of California, Los Angeles, Los Angeles, California, USA.
  • Rubbi L; Department of Cell, Molecular, and Developmental Biology, UCLA Life Sciences, University of California, Los Angeles, Los Angeles, California, USA.
  • Morselli M; Department of Cell, Molecular, and Developmental Biology, UCLA Life Sciences, University of California, Los Angeles, Los Angeles, California, USA.
  • Pellegrini M; Department of Cell, Molecular, and Developmental Biology, UCLA Life Sciences, University of California, Los Angeles, Los Angeles, California, USA.
  • Fiala M; Department of Cell, Molecular, and Developmental Biology, UCLA Life Sciences, University of California, Los Angeles, Los Angeles, California, USA; mfiala@ucla.edu.
FASEB J ; 31(10): 4359-4369, 2017 10.
Article em En | MEDLINE | ID: mdl-28634213
Macrophages (Mϕs) of patients with Alzheimer's disease and mild cognitive impairment (MCI) are defective in amyloid-ß1-42 (Aß) phagocytosis and have low resistance to apoptosis by Aß. Omega-3 fatty acids (ω-3s) in vitro and in vivo and the ω-3 mediator, resolvin D1, in vitro increase Aß phagocytosis by Mϕs of patients with MCI. We have investigated the unfolded protein response (UPR) to endoplasmic reticulum (ER) stress by Mϕs 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 Mϕ 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. In vitro treatment of Mϕs 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 vs. 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.
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Texto completo: 1 Base de dados: MEDLINE Assunto principal: Fragmentos de Peptídeos / Fagocitose / Ácidos Graxos Ômega-3 / Peptídeos beta-Amiloides / Disfunção Cognitiva / Estresse do Retículo Endoplasmático / Macrófagos Tipo de estudo: Observational_studies / Risk_factors_studies Idioma: En Revista: FASEB J Ano de publicação: 2017 Tipo de documento: Article País de afiliação: Estados Unidos
Texto completo
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Texto completo: 1 Base de dados: MEDLINE Assunto principal: Fragmentos de Peptídeos / Fagocitose / Ácidos Graxos Ômega-3 / Peptídeos beta-Amiloides / Disfunção Cognitiva / Estresse do Retículo Endoplasmático / Macrófagos Tipo de estudo: Observational_studies / Risk_factors_studies Idioma: En Revista: FASEB J Ano de publicação: 2017 Tipo de documento: Article País de afiliação: Estados Unidos