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Targeting liver X receptors in inflammation

Expert Opin Ther Targets. 2013 Aug;17(8):977-90. doi: 10.1517/14728222.2013.806490. Epub 2013 Jun 6.

Abstract

Introduction: The two oxysterol receptors, 'liver X receptors (LXRs)' LXRα and LXRβ, are amongst the emerging newer drug targets within the nuclear receptor family and targeting LXRs represents novel strategies needed for prevention and treatment of diseases where current therapeutics is inadequate.

Areas covered: This review discusses the current understanding of LXR biology with an emphasis on the molecular aspects of LXR signalling establishing their potential as drug targets. Recent advances of their transcriptional mechanisms in inflammatory pathways and their physiological roles in inflammation and immunity are described.

Expert opinion: The new discoveries of LXR-regulated inflammatory pathways have ignited new promises for LXRs as drug targets. The broad physiological roles of LXRs involve a high risk of unwanted side effects. Recent insights into LXR biology of the brain indicate a highly important role in neuronal development and a clinical trial testing an LXR agonist reported adverse neurological side effects. This suggests that drug development must focus on limiting the range of LXR signalling - possibly achieved through subtype, tissue specific, promoter specific or pathway specific activation of LXRs where a successful candidate drug must be carefully studied for its effect in the central nervous system.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Atherosclerosis / metabolism
  • Humans
  • Inflammation / metabolism*
  • Liver X Receptors
  • Orphan Nuclear Receptors / metabolism*
  • Signal Transduction

Substances

  • Liver X Receptors
  • NR1H3 protein, human
  • Orphan Nuclear Receptors