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Trends Pharmacol Sci. 2009 Apr;30(4):174-81. doi: 10.1016/j.tips.2009.01.002. Epub 2009 Mar 9.

The distinct roles of cyclooxygenase-1 and -2 in neuroinflammation: implications for translational research.

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  • 1Molecular Neuroscience Unit, Brain Physiology and Metabolism Section, National Institute on Aging, National Institutes of Health, Bethesda, MD 20892, USA.

Abstract

Cyclooxygenases (COX-1 and COX-2) are key enzymes in the conversion of arachidonic acid to prostaglandins and other lipid mediators. Because it can be induced by inflammatory stimuli, COX-2 has been classically considered as the most appropriate target for anti-inflammatory drugs. However, recent data indicate that COX-2 can mediate neuroprotection and that COX-1 is a major player in the neuroinflammatory process. We discuss the specific contributions of COX-1 and COX-2 in various neurodegenerative diseases and in models of neuroinflammation. We suggest that, owing to its predominant localization in microglia, COX-1 might be the major player in neuroinflammation, whereas COX-2, which is localized in neurons, might have a major role in models in which the neurons are directly challenged. Overall, the benefit of using COX-2 inhibitors should be carefully evaluated and COX-1 preferential inhibitors should be further investigated as a potential therapeutic approach in neurodegenerative diseases with an inflammatory component.

PMID:
19269697
PMCID:
PMC3379810
DOI:
10.1016/j.tips.2009.01.002
[PubMed - indexed for MEDLINE]
Free PMC Article
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