HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) All Versions of this Article: R800068-JLR200v1 50/Supplement/S400    most recent Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Bazan, N. G. Search for Related Content PubMed PubMed Citation Articles by Bazan, N. G. Related Collections Related Webpages Social Bookmarking                      What's this?

Journal of Lipid Research, Vol. 50, S400-S405, April 2009
Copyright © 2009 by American Society for Biochemistry and Molecular Biology

Lipids in Health and Disease

Neuroprotectin D1-mediated anti-inflammatory and survival signaling in stroke, retinal degenerations, and Alzheimer's disease

Nicolas G. Bazan¹

Neuroscience Center of Excellence and Department of Ophthalmology, School of Medicine, Louisiana State University Health Sciences Center, New Orleans, Louisiana

Supported by National Institutes of Health grants EY005121, NS046741, and P20 RR016816, the Foundation Fighting Blindness, and the Ernest C. and Yvette C. Villere Endowed Chair.

Published, JLR Papers in Press, November 18, 2008.

¹ To whom correspondence should be addressed. e-mail: nbazan{at}lsuhsc.edu

ABSTRACT

Docosahexaenoic acid (DHA), the main omega-3 fatty acid, is concentrated and avidly retained in membrane phospholipids of the nervous system. DHA is involved in brain and retina function, aging, and neurological and psychiatric/behavioral illnesses. Neuroprotectin D1 (NPD1), the first-identified stereoselective bioactive product of DHA, exerts neuroprotection in models of experimental stroke by down-regulating brain ischemia reperfusion (BIR)-induced leukocyte infiltration, proinflammatory signaling, and infarct size. Moreover, NPD1 inhibits cytokine-mediated cyclooxygenase-2 (COX-2) expression. Photoreceptor membranes display the highest content of DHA of any cell. Retinal pigment epithelial cells participate in the phagocytosis of the tips of photoreceptor cells (photoreceptor outer segment renewal). There is a DHA retrieval-intercellular mechanism between both types of cells that conserves this fatty acid during this process. NPD1 promotes homeostatic regulation of the integrity of these two cells, particularly during oxidative stress, and this protective signaling may be relevant in retinal degenerative diseases. Moreover, neurotrophins are NPD1-synthesis agonists, and NPD1 content is decreased in the CA1 region of the hippocampus of Alzheimer's patients. Overall, NPD1 promotes brain cell survival via the induction of antiapoptotic and neuroprotective gene-expression programs that suppress Aβ42 production and its neurotoxicity. Thus, NPD1 elicits potent cell-protective, anti-inflammatory, prosurvival repair signaling.

Supplementary key words 15-lipoxygenase-1 • retinal pigment epithelial cells • photoreceptor cells • docosanoids, Bcl-2 proteins • cyclooxygenase-2 • macular degenerations • retinitis pigmentosa • CA1 hippocampal region • docosahexaenoic acid

Abbreviations: AD, Alzheimer's disease; BIR, brain ischemia reperfusion; CEX-1, cytokine exodus protein-1; COX-2, cyclooxygenase-2; CNS, central nervous system; DHA, docosahexaenoic acid; IL-1β, interleukin-1β; NPD1, neuroprotectin D1; PLA₂, phospholipase A₂; RPE, retinal pigment epithelium; TNF, tumor necrosis factor

CiteULike    Complore    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?

Related Webpages: