Prostanoid signaling: Dual role for prostaglandin E2 in neurotoxicity

Dejan Milatovic, Thomas J. Montine, Michael Aschner

Research output: Contribution to journalReview articlepeer-review

44 Scopus citations

Abstract

The prostanoids, a naturally occurring subclass of eicosanoids, are lipid mediators generated through oxidative pathways from arachidonic acid. These cyclooxygenase metabolites, consisting of the prostaglandins (PG), prostacyclin and tromboxane, are released in response to a variety of physiological and pathological stimuli in almost all organs, including the brain. They are produced by various cell types and act upon targeted cells via specific G protein-coupled receptors. The existence of multiple receptors, cross-reactivity and coupling to different signal transduction pathways for each prostanoid, collectively establish their diverse effects. Notably, these effects can occur in functionally opposing directions within the same cell or organ. Prostaglandin E2 (PGE2) is the most versatile prostanoid because of its receptors, E Prostanoid (EP) receptor subtypes 1 through 4, its biological heterogeneity and its differential expression on neuronal and glial cells throughout the central nervous system. Since PGE2 plays an important role in processes associated with various neurological diseases, this review focuses on its dual neuroprotective and neurotoxic role in EP receptor subtype signaling pathways in different models of brain injury.

Original languageEnglish (US)
Pages (from-to)312-319
Number of pages8
JournalNeuroToxicology
Volume32
Issue number3
DOIs
StatePublished - Jun 1 2011
Externally publishedYes

Keywords

  • Arachidonic acid
  • E Prostanoid receptor
  • Neuroinflammation
  • Neurotoxicity
  • Prostaglandin E2

ASJC Scopus subject areas

  • Neuroscience(all)
  • Toxicology

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