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Prostaglandins Leukot Essent Fatty Acids. 2013 Oct;89(5):273-8. doi: 10.1016/j.plefa.2013.08.008. Epub 2013 Sep 16.

Alterations of brain eicosanoid synthetic pathway in multiple sclerosis and in animal models of demyelination: role of cyclooxygenase-2.

Author information

1
Molecular Neuroscience Unit, Brain Physiology and Metabolism Section, National Institute on Aging, National Institutes of Health, 20892 Bethesda, MD, USA. Electronic address: palumbosar@gmail.com.

Abstract

Inflammation is a physiological response to exogenous and endogenous stimuli and, together with demyelination and immune system activation, is one of the key features of multiple sclerosis (MS). Arachidonic acid (AA) metabolism by cyclooxygenase (COX) and lipoxygenase (LO) enzymes leads to the production of proinflammatory eicosanoids, and stimulates cytokine production and activation of microglia and astrocytes, thereby contributing to MS pathology. Current therapies target the immune system but do not specifically target AA-related inflammatory pathway. Corticosteroids and non-steroidal anti-inflammatory drugs (NSAIDs) are frequently associated with immunomodulatory therapies to treat flu-like adverse effects. Few clinical and mounting preclinical data in MS show that AA metabolism contributes to immune system activation, demyelination and motor disabilities, and administration of NSAIDs reduces these symptoms. The beneficial effect of NSAIDs seems to be a prerogative of COX-2 selective inhibitors and suggests that NSAIDs selective for COX-2 may be more effective than mixed COX-1/2 inhibitors.

KEYWORDS:

Arachidonic acid; Cuprizone; Cyclooxigenases; EAE; Multiple sclerosis; NSAID; Theiler's virus

PMID:
24095587
DOI:
10.1016/j.plefa.2013.08.008
[Indexed for MEDLINE]

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