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 Gotlinger, Charles N. Serhan, Nicolas G. Bazan

Research output: Contribution to journalArticle

618 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)2774-2783
Number of pages10
JournalJournal of Clinical Investigation
Volume115
Issue number10
DOIs
StatePublished - Oct 1 2005

ASJC Scopus subject areas

  • Medicine(all)

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    Lukiw, W. J., Cui, J. G., Marcheselli, V. L., Bodker, M., Botkjaer, A., Gotlinger, K., Serhan, C. N., & Bazan, N. G. (2005). A role for docosahexaenoic acid-derived neuroprotectin D1 in neural cell survival and Alzheimer disease. Journal of Clinical Investigation, 115(10), 2774-2783. https://doi.org/10.1172/JCI25420