A Role for Docosahexaenoic Acid-derived Neuroprotectin D1 in Neural Cell Survival and Alzheimer Disease

Overview

Journal J Clin Invest

Specialty General Medicine

Date 2005 Sep 10

PMID 16151530

Citations 300

Authors

Walter J Lukiw

Jian-Guo Cui

Victor L Marcheselli

Merete Bodker

Anja Botkjaer

Katherine Gotlinger

Charles N Serhan

Nicolas G Bazan

Affiliations

Soon will be listed here.

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-beta (Abeta) 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 Abeta42-triggered activation of proinflammatory genes while upregulating the antiapoptotic genes encoding Bcl-2, Bcl-xl, and Bfl-1(A1). Soluble amyloid precursor protein-alpha 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 Abeta42-induced neurotoxicity.

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References

Xu J, Chen S, Ahmed S, Chen H, Ku G, Goldberg M . Amyloid-beta peptides are cytotoxic to oligodendrocytes. J Neurosci. 2001; 21(1):RC118. PMC: 6762453. View

Liao Y, Wang B, Cheng H, Kuo L, Wolfe M . Tumor necrosis factor-alpha, interleukin-1beta, and interferon-gamma stimulate gamma-secretase-mediated cleavage of amyloid precursor protein through a JNK-dependent MAPK pathway. J Biol Chem. 2004; 279(47):49523-32. DOI: 10.1074/jbc.M402034200. View

Ikemoto A, Ohishi M, Sato Y, Hata N, Misawa Y, Fujii Y . Reversibility of n-3 fatty acid deficiency-induced alterations of learning behavior in the rat: level of n-6 fatty acids as another critical factor. J Lipid Res. 2001; 42(10):1655-63. View

Zhang Y, McLaughlin R, Goodyer C, Leblanc A . Selective cytotoxicity of intracellular amyloid beta peptide1-42 through p53 and Bax in cultured primary human neurons. J Cell Biol. 2002; 156(3):519-29. PMC: 2173346. DOI: 10.1083/jcb.200110119. View

Yamada T, Kadekaru H, Matsumoto S, Inada H, Tanabe M, Moriguchi E . Prevalence of dementia in the older Japanese-Brazilian population. Psychiatry Clin Neurosci. 2002; 56(1):71-5. DOI: 10.1046/j.1440-1819.2002.00931.x. View

Cheng G, Yu Z, Zhou D, Mattson M . Phosphatidylinositol-3-kinase-Akt kinase and p42/p44 mitogen-activated protein kinases mediate neurotrophic and excitoprotective actions of a secreted form of amyloid precursor protein. Exp Neurol. 2002; 175(2):407-14. DOI: 10.1006/exnr.2002.7920. View

Bazan N, Lukiw W . Cyclooxygenase-2 and presenilin-1 gene expression induced by interleukin-1beta and amyloid beta 42 peptide is potentiated by hypoxia in primary human neural cells. J Biol Chem. 2002; 277(33):30359-67. DOI: 10.1074/jbc.M203201200. View

Montine T, Neely M, Quinn J, Beal M, Markesbery W, Roberts L . Lipid peroxidation in aging brain and Alzheimer's disease. Free Radic Biol Med. 2002; 33(5):620-6. DOI: 10.1016/s0891-5849(02)00807-9. View

Grant W, Campbell A, Itzhaki R, Savory J . The significance of environmental factors in the etiology of Alzheimer's disease. J Alzheimers Dis. 2002; 4(3):179-89. DOI: 10.3233/jad-2002-4308. View

10.

Colangelo V, Schurr J, Ball M, Pelaez R, Bazan N, Lukiw W . Gene expression profiling of 12633 genes in Alzheimer hippocampal CA1: transcription and neurotrophic factor down-regulation and up-regulation of apoptotic and pro-inflammatory signaling. J Neurosci Res. 2002; 70(3):462-73. DOI: 10.1002/jnr.10351. View

11.

Barberger-Gateau P, Letenneur L, Deschamps V, Peres K, Dartigues J, Renaud S . Fish, meat, and risk of dementia: cohort study. BMJ. 2002; 325(7370):932-3. PMC: 130057. DOI: 10.1136/bmj.325.7370.932. View

12.

Webster N, Green K, Peers C, Vaughan P . Altered processing of amyloid precursor protein in the human neuroblastoma SH-SY5Y by chronic hypoxia. J Neurochem. 2002; 83(6):1262-71. DOI: 10.1046/j.1471-4159.2002.01236.x. View

13.

Catalan J, Moriguchi T, Slotnick B, Murthy M, Greiner R, Salem Jr N . Cognitive deficits in docosahexaenoic acid-deficient rats. Behav Neurosci. 2002; 116(6):1022-31. DOI: 10.1037//0735-7044.116.6.1022. View

14.

Kim H, Chae S, Chromy B, Lee S, Park Y, Klein W . Selective neuronal degeneration induced by soluble oligomeric amyloid beta protein. FASEB J. 2002; 17(1):118-20. DOI: 10.1096/fj.01-0987fje. View

15.

Hong S, Gronert K, Devchand P, Moussignac R, Serhan C . Novel docosatrienes and 17S-resolvins generated from docosahexaenoic acid in murine brain, human blood, and glial cells. Autacoids in anti-inflammation. J Biol Chem. 2003; 278(17):14677-87. DOI: 10.1074/jbc.M300218200. View

16.

Lahiri D, Chen D, Vivien D, Ge Y, Greig N, Rogers J . Role of cytokines in the gene expression of amyloid beta-protein precursor: identification of a 5'-UTR-binding nuclear factor and its implications in Alzheimer's disease. J Alzheimers Dis. 2003; 5(2):81-90. DOI: 10.3233/jad-2003-5203. View

17.

Morris M, Evans D, Bienias J, Tangney C, Bennett D, Wilson R . Consumption of fish and n-3 fatty acids and risk of incident Alzheimer disease. Arch Neurol. 2003; 60(7):940-6. DOI: 10.1001/archneur.60.7.940. View

18.

Hong H, Hwang E, Sim H, Cho H, Boo J, Oh S . Interferon gamma stimulates beta-secretase expression and sAPPbeta production in astrocytes. Biochem Biophys Res Commun. 2003; 307(4):922-7. DOI: 10.1016/s0006-291x(03)01270-1. View

19.

McGeer E, McGeer P . Inflammatory processes in Alzheimer's disease. Prog Neuropsychopharmacol Biol Psychiatry. 2003; 27(5):741-9. DOI: 10.1016/S0278-5846(03)00124-6. View

20.

Pelvig D, Pakkenberg H, Regeur L, Oster S, Pakkenberg B . Neocortical glial cell numbers in Alzheimer's disease. A stereological study. Dement Geriatr Cogn Disord. 2003; 16(4):212-9. DOI: 10.1159/000072805. View