Sporadic late-onset Alzheimer disease (LOAD) preceded by mild cognitive impairment (MCI) is the most common type of dementia. Long-term studies of immunity to pathogenic amyloid-β (Aβ) in LOAD are lacking. Innate immunity of LOAD patients is malfunctioning in phagocytosis and degradation of Aβ and LOAD patients' macrophage transcriptome and metabolome are deregulated. We previously showed omega-3 fatty acid (ω-3)-mediated repair of unfolded protein response and here we show much broader transcriptomic effects. ω-3 treatment in vitro and ω-3 supplementation by the drink Smartfish (SMF) in vivo increased the transcripts of the genes and pathways of immunity, glycolysis, tricarboxylic acid cycle, OX-PHOS, nicotinamide dinucleotide (NAD+ ) synthesis, and reversed the defects in Aβ phagocytosis. In both peripheral blood mononuclear cells (PBMC) and macrophages, ω-3 increased ATP-linked oxygen consumption rate (OCR) and ω-3 with carnitine was superior to ω-3. ω-3 treatment in vitro and supplementation by the ω-3 drink SMF in vivo rescued macrophage phagocytosis when glycolysis or glycosylation were blocked. ω-3 provide flexible energy for immune clearance of the brain throughout the diurnal cycle, even in hypo- or hyper-glycemia. In certain LOAD patients, ω-3 may delay progression to dementia.

Omega-3 fatty acids increase OXPHOS energy for immune therapy of Alzheimer disease patients / Lau, Ycc; Ding, Ja; Simental, A; Mirzoyan, H; Lee, W; Diamante, G; Cely, I; Tran, M; Morselli, M; Dang, J; Kaczor-Urbanowicz, Ke; Sayre, J; Stiles, L; Yang, X; Pellegrini, M; Fiala, M.. - In: FASEB JOURNAL. - ISSN 1530-6860. - (2020). [10.1096/fj.202000669RR]

Omega-3 fatty acids increase OXPHOS energy for immune therapy of Alzheimer disease patients.

Morselli M;
2020-01-01

Abstract

Sporadic late-onset Alzheimer disease (LOAD) preceded by mild cognitive impairment (MCI) is the most common type of dementia. Long-term studies of immunity to pathogenic amyloid-β (Aβ) in LOAD are lacking. Innate immunity of LOAD patients is malfunctioning in phagocytosis and degradation of Aβ and LOAD patients' macrophage transcriptome and metabolome are deregulated. We previously showed omega-3 fatty acid (ω-3)-mediated repair of unfolded protein response and here we show much broader transcriptomic effects. ω-3 treatment in vitro and ω-3 supplementation by the drink Smartfish (SMF) in vivo increased the transcripts of the genes and pathways of immunity, glycolysis, tricarboxylic acid cycle, OX-PHOS, nicotinamide dinucleotide (NAD+ ) synthesis, and reversed the defects in Aβ phagocytosis. In both peripheral blood mononuclear cells (PBMC) and macrophages, ω-3 increased ATP-linked oxygen consumption rate (OCR) and ω-3 with carnitine was superior to ω-3. ω-3 treatment in vitro and supplementation by the ω-3 drink SMF in vivo rescued macrophage phagocytosis when glycolysis or glycosylation were blocked. ω-3 provide flexible energy for immune clearance of the brain throughout the diurnal cycle, even in hypo- or hyper-glycemia. In certain LOAD patients, ω-3 may delay progression to dementia.
2020
Omega-3 fatty acids increase OXPHOS energy for immune therapy of Alzheimer disease patients / Lau, Ycc; Ding, Ja; Simental, A; Mirzoyan, H; Lee, W; Diamante, G; Cely, I; Tran, M; Morselli, M; Dang, J; Kaczor-Urbanowicz, Ke; Sayre, J; Stiles, L; Yang, X; Pellegrini, M; Fiala, M.. - In: FASEB JOURNAL. - ISSN 1530-6860. - (2020). [10.1096/fj.202000669RR]
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11381/2901228
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