A role for docosahexaenoic acid-derived neuroprotectin D1 in neural cell survival and Alzheimer disease

作者：Lukiw WJ; Cui JG; Marcheselli VL; Bodker M; Botkjaer A; Gotlinger K; Serhan CN; Bazan NG^*

来源：Journal of Clinical Investigation, 2005, 115(10): 2774-2783.

DOI：10.1172/JCI25420

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.

• 出版日期2005-10