Liver X receptors in lipid metabolism: opportunities for drug discovery

Nat Rev Drug Discov. 2014 Jun;13(6):433-44. doi: 10.1038/nrd4280. Epub 2014 May 16.

Abstract

The liver X receptors (LXRs) are pivotal regulators of lipid homeostasis in mammals. These transcription factors control the expression of a battery of genes involved in the uptake, transport, efflux and excretion of cholesterol in a tissue-dependent manner. The identification of the LXRs, and an increased understanding of the mechanisms by which LXR signalling regulates lipid homeostasis in different tissues (including the liver, intestine and brain), has highlighted new opportunities for therapeutic intervention in human metabolism. New strategies for the pharmacological manipulation of LXRs and their target genes offer promise for the treatment of human diseases in which lipids have a central role, including atherosclerosis and Alzheimer's disease.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Alzheimer Disease / drug therapy
  • Alzheimer Disease / metabolism
  • Alzheimer Disease / prevention & control
  • Animals
  • Atherosclerosis / drug therapy
  • Atherosclerosis / metabolism
  • Atherosclerosis / prevention & control
  • Brain / drug effects
  • Brain / metabolism
  • Clinical Trials as Topic
  • Drug Design*
  • Drug Discovery*
  • Drug Evaluation, Preclinical
  • Drugs, Investigational / chemistry
  • Drugs, Investigational / pharmacology*
  • Drugs, Investigational / therapeutic use
  • Humans
  • Hypolipidemic Agents / adverse effects
  • Hypolipidemic Agents / chemistry
  • Hypolipidemic Agents / pharmacology*
  • Hypolipidemic Agents / therapeutic use
  • Intestinal Mucosa / metabolism
  • Intestines / drug effects
  • Lipid Metabolism / drug effects*
  • Liver / drug effects
  • Liver / metabolism
  • Liver X Receptors
  • Molecular Targeted Therapy / adverse effects
  • Nerve Tissue Proteins / antagonists & inhibitors
  • Nerve Tissue Proteins / metabolism
  • Neurons / drug effects
  • Neurons / metabolism
  • Nootropic Agents / adverse effects
  • Nootropic Agents / chemistry
  • Nootropic Agents / pharmacology*
  • Nootropic Agents / therapeutic use
  • Orphan Nuclear Receptors / antagonists & inhibitors*
  • Orphan Nuclear Receptors / metabolism
  • Protein Isoforms / antagonists & inhibitors
  • Protein Isoforms / metabolism
  • Signal Transduction / drug effects

Substances

  • Drugs, Investigational
  • Hypolipidemic Agents
  • Liver X Receptors
  • Nerve Tissue Proteins
  • Nootropic Agents
  • Orphan Nuclear Receptors
  • Protein Isoforms