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

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

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Docosahexaenoic Acids
Cell Survival
Alzheimer Disease
Hippocampus
Brain
Arachidonate 15-Lipoxygenase
Cytosolic Phospholipases A2
bcl-2 Genes
Occipital Lobe
Essential Fatty Acids
Amyloid beta-Protein Precursor
Omega-3 Fatty Acids
Thalamus
Amyloid
Transcriptional Activation
protectin D1
Cytokines
Gene Expression
Enzymes

ASJC Scopus subject areas

  • Medicine(all)

Cite this

Lukiw, W. J., Cui, J. G., Marcheselli, V. L., Bodker, M., Botkjaer, A., Gotlinger, K., ... 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

A role for docosahexaenoic acid-derived neuroprotectin D1 in neural cell survival and Alzheimer disease. / Lukiw, Walter J.; Cui, Jian Guo; Marcheselli, Victor L.; Bodker, Merete; Botkjaer, Anja; Gotlinger, Katherine; Serhan, Charles N.; Bazan, Nicolas G.

In: Journal of Clinical Investigation, Vol. 115, No. 10, 01.10.2005, p. 2774-2783.

Research output: Contribution to journalArticle

Lukiw, WJ, Cui, JG, Marcheselli, VL, Bodker, M, Botkjaer, A, Gotlinger, K, Serhan, CN & Bazan, NG 2005, 'A role for docosahexaenoic acid-derived neuroprotectin D1 in neural cell survival and Alzheimer disease', Journal of Clinical Investigation, vol. 115, no. 10, pp. 2774-2783. https://doi.org/10.1172/JCI25420
Lukiw, Walter J. ; Cui, Jian Guo ; Marcheselli, Victor L. ; Bodker, Merete ; Botkjaer, Anja ; Gotlinger, Katherine ; Serhan, Charles N. ; Bazan, Nicolas G. / A role for docosahexaenoic acid-derived neuroprotectin D1 in neural cell survival and Alzheimer disease. In: Journal of Clinical Investigation. 2005 ; Vol. 115, No. 10. pp. 2774-2783.
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