A role for docosahexaenoic acid-derived neuroprotectin D1 in neural cell survival and Alzheimer disease.
Walter J. Lukiw,Jian Guo Cui,Victor L. Marcheselli,Merete Bodker,Anja Botkjaer,Katherine H. Gotlinger,Charles N. Serhan,Nicolas G. Bazan +7 more
TLDR
Results indicate that NPD1 promotes brain cell survival via the induction of antiapoptotic and neuroprotective gene-expression programs that suppress Abeta42-induced neurotoxicity.Abstract:
Deficiency in docosahexaenoic acid (DHA), a brain-essential omega-3 fatty acid, is associated with cognitive decline. Here we report that, in cytokine-stressed human neural cells, DHA attenuates amyloid-β (Aβ) secretion, an effect accompanied by the formation of NPD1, a novel, DHA-derived 10,17S-docosatriene. DHA and NPD1 were reduced in Alzheimer disease (AD) hippocampal cornu ammonis region 1, but not in the thalamus or occipital lobes from the same brains. The expression of key enzymes in NPD1 biosynthesis, cytosolic phospholipase A2 and 15-lipoxygenase, was altered in AD hippocampus. NPD1 repressed Aβ42-triggered activation of proinflammatory genes while upregulating the antiapoptotic genes encoding Bcl-2, Bcl-xl, and Bfl-1(A1). Soluble amyloid precursor protein-α stimulated NPD1 biosynthesis from DHA. These results indicate that NPD1 promotes brain cell survival via the induction of antiapoptotic and neuroprotective gene-expression programs that suppress Aβ42-induced neurotoxicity.read more
Citations
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Neuroinflammation in Alzheimer's disease
Michael T. Heneka,Monica J. Carson,Joseph El Khoury,Gary E. Landreth,Frederic Brosseron,Douglas L. Feinstein,Andreas H. Jacobs,Tony Wyss-Coray,Tony Wyss-Coray,Javier Vitorica,Richard M. Ransohoff,Karl Herrup,Sally A. Frautschy,Bente Finsen,Guy C. Brown,Alexei Verkhratsky,Alexei Verkhratsky,Alexei Verkhratsky,Koji Yamanaka,Jari Koistinaho,Eicke Latz,Eicke Latz,Annett Halle,Gabor C. Petzold,Terrence Town,Dave Morgan,Mari L. Shinohara,V. Hugh Perry,Clive Holmes,Clive Holmes,Nicolas G. Bazan,David J. Brooks,Stéphane Hunot,Bertrand Joseph,Nikolaus Deigendesch,Olga Garaschuk,Erik Boddeke,Charles A. Dinarello,John C.S. Breitner,Greg M. Cole,Douglas T. Golenbock,Markus P. Kummer +41 more
TL;DR: Genome-wide analysis suggests that several genes that increase the risk for sporadic Alzheimer's disease encode factors that regulate glial clearance of misfolded proteins and the inflammatory reaction.
Journal ArticleDOI
Resolving inflammation : dual anti-inflammatory and pro-resolution lipid mediators
TL;DR: New cellular and molecular mechanisms for the resolution of inflammation are presented, revealing key roles for eicosanoids, such as lipoxins, and recently discovered families of endogenous chemical mediators, termed resolvins and protectins, which have anti-inflammatory and pro-resolution properties.
Journal ArticleDOI
Pro-resolving lipid mediators are leads for resolution physiology
TL;DR: The mechanisms of specialized pro-resolving mediators and omega-3 essential fatty acid pathways that could help us to understand their physiological functions are covered.
Journal ArticleDOI
Polyunsaturated fatty acids and their metabolites in brain function and disease
Richard P. Bazinet,Sophie Layé +1 more
TL;DR: Diet and drugs targeting PUFAs may lead to novel therapeutic approaches for the prevention and treatment of brain disorders, including Alzheimer's disease and major depression.
Journal ArticleDOI
Resolution Phase of Inflammation: Novel Endogenous Anti-Inflammatory and Proresolving Lipid Mediators and Pathways
TL;DR: Given the potent actions of lipoxins, resolvins, and protectins in models of human disease, deficiencies in resolution pathways may contribute to many diseases and offer exciting new potential for therapeutic control via resolution.
References
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Journal ArticleDOI
Novel Docosanoids Inhibit Brain Ischemia-Reperfusion-mediated Leukocyte Infiltration and Pro-inflammatory Gene Expression
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