Targeting liver X receptors in inflammation

Knut R. Steffensen, Tomas Jakobsson, Jan Åke Gustafsson

Research output: Contribution to journalReview article

42 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)977-990
Number of pages14
JournalExpert Opinion on Therapeutic Targets
Volume17
Issue number8
DOIs
StatePublished - Aug 2013

Keywords

  • Inflammation
  • Liver X receptor
  • Oxysterol receptor
  • Transrepression

ASJC Scopus subject areas

  • Drug Discovery
  • Pharmacology
  • Clinical Biochemistry
  • Molecular Medicine

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