title: Role of docosahexaenoic acid in the modulation of glial cells in Alzheimer's disease.
abstract: Docosahexaenoic acid (DHA) is an omega-3 (ω-3) long-chain polyunsaturated fatty acid (LCPUFA) relevant for brain function. It has largely been explored as a potential candidate to treat Alzheimer's disease (AD). Clinical evidence favors a role for DHA in the improvement of cognition in very early stages of the AD. In response to stress or damage, DHA generates oxygenated derivatives called docosanoids that can activate the peroxisome proliferator-activated receptor γ (PPARγ). In conjunction with activated retinoid X receptors (RXR), PPARγ modulates inflammation, cell survival, and lipid metabolism. As an early event in AD, inflammation is associated with an excess of amyloid β peptide (Aβ) that contributes to neural insult. Glial cells are recognized to be actively involved during AD, and their dysfunction is associated with the early appearance of this pathology. These cells give support to neurons, remove amyloid β peptides from the brain, and modulate inflammation. Since DHA can modulate glial cell activity, the present work reviews the evidence about this modulation as well as the effect of docosanoids on neuroinflammation and in some AD models. The evidence supports PPARγ as a preferred target for gene modulation. The effective use of DHA and/or its derivatives in a subgroup of people at risk of developing AD is discussed.
authors.affiliation: Departamento de Biología, Facultad de Química, Universidad Nacional Autónoma de México, Ciudad Universitaria, 04510, México, DF, México.|Laboratorio de Farmacología, Subdirección de Investigación Básica, Instituto Nacional de Cancerología (INCan), Av. San Fernando #22, Tlalpan 14080, Apartado Postal 22026, México, DF, México.
authors.forename: David
authors.initials: D
authors.lastname: Heras-Sandoval
authors.affiliation: Departamento de Biología, Facultad de Química, Universidad Nacional Autónoma de México, Ciudad Universitaria, 04510, México, DF, México.
authors.forename: José
authors.initials: J
authors.lastname: Pedraza-Chaverri
authors.affiliation: Laboratorio de Farmacología, Subdirección de Investigación Básica, Instituto Nacional de Cancerología (INCan), Av. San Fernando #22, Tlalpan 14080, Apartado Postal 22026, México, DF, México. jazminmarlen@gmail.com.
authors.forename: Jazmin M
authors.identifier: http://orcid.org/0000-0002-5766-2684
authors.initials: JM
authors.lastname: Pérez-Rojas
mesh_terms: D000544:Alzheimer Disease / Q000235:genetics / Q000473:pathology*; D016229:Amyloid beta-Peptides / Q000378:metabolism; D000818:Animals; D004281:Docosahexaenoic Acids / Q000494:pharmacology*; D006801:Humans; D009457:Neuroglia / Q000187:drug effects*; D047495:PPAR gamma / Q000187:drug effects
chemical_list: D016229:Amyloid beta-Peptides; D047495:PPAR gamma; D004281:Docosahexaenoic Acids
keywords: Alzheimer’s disease (AD); Amyloid β peptide (Aβ); Docosahexaenoic acid (DHA); Glial cells; Neuroinflammation; Neuroprotectin D1 (NPD1); Resolvin D1 (RvD1)