title: Docosahexaenoic acid prevents neuronal apoptosis induced by soluble amyloid-beta oligomers.
abstract: A growing body of evidence supports the notion that soluble oligomers of amyloid-beta (Abeta) peptide interact with the neuronal plasma membrane, leading to cell injury and inducing death-signalling pathways that could account for the increased neurodegeneration occurring in Alzheimer's disease (AD). Docosahexaenoic acid (DHA, C22:6, n-3) is an essential polyunsaturated fatty acid in the CNS and has been shown in several epidemiological and in vivo studies to have protective effects against AD and cognitive alterations. However, the molecular mechanisms involved remain unknown. We hypothesized that DHA enrichment of plasma membranes could protect neurones from apoptosis induced by soluble Abeta oligomers. DHA pre-treatment was observed to significantly increase neuronal survival upon Abeta treatment by preventing cytoskeleton perturbations, caspase activation and apoptosis, as well as by promoting extracellular signal-related kinase (ERK)-related survival pathways. These data suggest that DHA enrichment probably induces changes in neuronal membrane properties with functional outcomes, thereby increasing protection from soluble Abeta oligomers. Such neuroprotective effects could be of major interest in the prevention of AD and other neurodegenerative diseases.
authors.affiliation: Jeune Equipe Lipidomix, Institut National Polytechnique de Lorraine, Laboratoire Médecine et Thérapeutique Moléculaire, Vandoeuvre-lès-Nancy, France.
authors.forename: Sabrina
authors.initials: S
authors.lastname: Florent
authors.forename: Catherine
authors.initials: C
authors.lastname: Malaplate-Armand
authors.forename: Ihsen
authors.initials: I
authors.lastname: Youssef
authors.forename: Badreddine
authors.initials: B
authors.lastname: Kriem
authors.forename: Violette
authors.initials: V
authors.lastname: Koziel
authors.forename: Marie-Christine
authors.initials: MC
authors.lastname: Escanyé
authors.forename: Alexandre
authors.initials: A
authors.lastname: Fifre
authors.forename: Isabelle
authors.initials: I
authors.lastname: Sponne
authors.forename: Brigitte
authors.initials: B
authors.lastname: Leininger-Muller
authors.forename: Jean-Luc
authors.initials: JL
authors.lastname: Olivier
authors.forename: Thierry
authors.initials: T
authors.lastname: Pillot
authors.forename: Thierry
authors.initials: T
authors.lastname: Oster
mesh_terms: D016229:Amyloid beta-Peptides / Q000737:chemistry* / Q000494:pharmacology*; D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D020169:Caspases / Q000378:metabolism; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000166:cytology; D003599:Cytoskeleton / Q000187:drug effects; D003600:Cytosol / Q000201:enzymology; D004281:Docosahexaenoic Acids / Q000494:pharmacology*; D004789:Enzyme Activation / Q000187:drug effects; D015525:Fatty Acids, Omega-3 / Q000494:pharmacology; D009474:Neurons / Q000502:physiology*; D018696:Neuroprotective Agents / Q000494:pharmacology*; D009836:Oligodendroglia / Q000502:physiology; D018384:Oxidative Stress / Q000187:drug effects; D010741:Phospholipases A / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D012995:Solubility
chemical_list: D016229:Amyloid beta-Peptides; D015525:Fatty Acids, Omega-3; D018696:Neuroprotective Agents; D004281:Docosahexaenoic Acids; D010741:Phospholipases A; D020169:Caspases