Journal
JOURNAL OF CLINICAL INVESTIGATION
Volume 115, Issue 10, Pages 2774-2783Publisher
AMER SOC CLINICAL INVESTIGATION INC
DOI: 10.1172/JCI25420
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Funding
- NCRR NIH HHS [RR16816, P20 RR016816] Funding Source: Medline
- NIA NIH HHS [AG18031, R01 AG018031] Funding Source: Medline
- NIGMS NIH HHS [R01 GM038765, GM38765, R37 GM038765] Funding Source: Medline
- NINDS NIH HHS [NS23002, R01 NS046741, NS46741, R01 NS023002] Funding Source: Medline
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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-P (AP) 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 A(2) and 15-lipoxygenase, was altered in AD hippocampus. NPD1 repressed A beta 42-triggered activation of proinflammatory genes while upregulating the antiapoptotic genes encoding Bcl-2, Bcl-xl, and Bfl-1(A1). Soluble amyloid precursor protein-a 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 A beta 42-induced neurotoxicity.
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