TY - JOUR
T1 - Omega-3 fatty acids increase the unfolded protein response and improve amyloid-β phagocytosis by macrophages of patients with mild cognitive impairment
AU - Olivera-Perez, Henry M.
AU - Lam, Larry
AU - Dang, Johnny
AU - Jiang, Weilan
AU - Rodriguez, Fabian
AU - Rigali, Elizabeth
AU - Weitzman, Sarah
AU - Porter, Verna
AU - Rubbi, Liudmilla
AU - Morselli, Marco
AU - Pellegrini, Matteo
AU - Fiala, Milan
N1 - Publisher Copyright:
© FASEB.
PY - 2017/10
Y1 - 2017/10
N2 - Macrophages (Mφs) 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 (ω-3s) in vitro and in vivo and the ω-3 mediator, resolvin D1, in vitro increase Aβ 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, Aβ 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 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 ω-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.
AB - Macrophages (Mφs) 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 (ω-3s) in vitro and in vivo and the ω-3 mediator, resolvin D1, in vitro increase Aβ 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, Aβ 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 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 ω-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.
UR - http://www.scopus.com/inward/record.url?scp=85030625909&partnerID=8YFLogxK
U2 - 10.1096/fj.201700290R
DO - 10.1096/fj.201700290R
M3 - Article
C2 - 28634213
AN - SCOPUS:85030625909
SN - 0892-6638
VL - 31
SP - 4359
EP - 4369
JO - FASEB Journal
JF - FASEB Journal
IS - 10
ER -