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
Department of Cell, Molecular, and Developmental Biology, UCLA Life Sciences, University of California, Los Angeles, Los Angeles, California, USA.
Department of Neurology, UCLA School of Medicine, University of California, Los Angeles, Los Angeles, California, USA.
FASEB J. 2017 Oct;31(10):4359-4369. doi: 10.1096/fj.201700290R. Epub 2017 Jun 20.
Macrophages (Mϕs) of patients with Alzheimer's disease and mild cognitive impairment (MCI) are defective in amyloid-β (Aβ) phagocytosis and have low resistance to apoptosis by Aβ. Omega-3 fatty acids (ω-3s) and and the ω-3 mediator, resolvin D1, 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. 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 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-β phagocytosis by macrophages of patients with mild cognitive impairment.
阿尔茨海默病和轻度认知障碍（MCI）患者的巨噬细胞（Mϕ）在β淀粉样蛋白（Aβ）吞噬方面存在缺陷，并且对Aβ诱导的细胞凋亡抵抗力较低。ω-3脂肪酸（ω-3s）以及ω-3介质——消退素D1，可增加MCI患者Mϕ的Aβ吞噬作用。我们在一项针对鱼类来源的、补充ω-3的MCI患者的纵向研究中，研究了Mϕ对内质网（ER）应激的未折叠蛋白反应（UPR）。随着时间的推移，载脂蛋白E（ApoE）e3/e3亚组的患者蛋白激酶RNA样内质网激酶（PERK）表达增加、Aβ吞噬作用增强、呈现中间型M1-M2 Mϕ类型，且简易精神状态检查表（MMSE）每年变化率为+1.8分，而ApoEe3/e4亚组的患者个体结果存在差异，MMSE每年变化率为-3.2分。用鱼类来源的ω-3乳剂处理Mϕ可增加Aβ吞噬作用、PERK表达以及UPR RNA特征，并降低ER应激特征。UPR特征中增强的基因包括伴侣蛋白、凝集素、折叠酶和N-连接糖基化酶。总之，鱼类来源的ω-3s增加细胞保护基因并减少促凋亡基因，改善Aβ的免疫清除，并且与ApoEe3/e3和ApoEe3/e4患者的MMSE变化率改善相关。——奥利韦拉-佩雷斯，H.M.，林，L.，当，J.，江，W.，罗德里格斯，F.，里加利，E.，韦茨曼，S.，波特，V.，鲁比，L.，莫尔塞利，M.，佩莱格里尼，M.，菲亚拉，M. ω-3脂肪酸增加未折叠蛋白反应并改善轻度认知障碍患者巨噬细胞的β淀粉样蛋白吞噬作用
