Omega-3 fatty acids increase the unfolded protein response and improve amyloid-{beta} phagocytosis by macrophages of patients with mild cognitive impairment [Research]

Macrophages (Ms) of patients with Alzheimer’s disease and mild cognitive impairment (MCI) are defective in amyloid-β1-42 (Aβ) phagocytosis and have low resistance to apoptosis by Aβ. Omega-3 fatty acids (-3s) in vitro and in vivo and the -3 mediator, resolvin D1, in vitro increase Aβ phagocytosis by Ms of patients with MCI. We have investigated the unfolded protein response (UPR) to endoplasmic reticulum (ER) stress by Ms in a longitudinal study of fish-derived, -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, Aβ phagocytosis, intermediate M1-M2 M 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 Ms by fish-derived -3 emulsion increased Aβ 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 -3s increase cytoprotective genes and decrease proapoptotic genes, improve immune clearance of Aβ, 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.,...

Source: FASEB Journal - September 28, 2017 Category: Biology Authors: 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. Tags: Research Source Type: research