Omega-3 fatty acids increase the unfolded protein response and improve amyloid-? phagocytosis by macrophages of patients with mild cognitive impairment.

ABSTRACT: Macrophages (M?s) of patients with Alzheimer's disease and mild cognitive impairment (MCI) are defective in amyloid-?1-42 (A?) phagocytosis and have low resistance to apoptosis by A?. Omega-3 fatty acids (?-3s) in vitro and in vivo and the ?-3 mediator, resolvin D1, in vitro increase A? phagocytosis by M?s of patients with MCI. We have investigated the unfolded protein response (UPR) to endoplasmic reticulum (ER) stress by M?s 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, A? 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 M?s by fish-derived ?-3 emulsion increased A? 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 A?, 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-? phagocytosis by macrophages of patients with mild cognitive impairment.

SUBMITTER: Olivera-Perez HM 

PROVIDER: S-EPMC5602894 | biostudies-other | 2017 Oct

REPOSITORIES: biostudies-other