title: Targeting liver X receptors in human health: deadlock or promising trail?
abstract: BACKGROUND
  Liver X receptors (LXR) are transcription factors that belong to the nuclear receptor superfamily. Natural derivatives of cholesterol, known as oxysterols, have been identified as agonistic ligands of LXR. They are thus mainly considered to be intracellular cholesterol 'sensors' whose activation leads to decreased plasma cholesterol. Their implication in other physiologic processes currently prevents their use as therapeutic targets, because of potentially deleterious side effects.
  
  
  METHODS
  The various LXR agonists and antagonists, along with the physiological functions of LXR. Putative clinical targets including atherosclerosis, diabetes, Alzheimer's disease, skin disorders, reproductive disorders and cancer.
  
  
  CONCLUSIONS
  LXR are promising pharmacological targets because of the high potential to develop ligands owing to the variety of natural or synthetic agonists. Three aspects should be developed to select a LXR-ligand for treatment of human disease: bio-availability; isoform specificity; tissue specificity. This will allow the development of selective liver X modulators (SLiMs). The challenge is to overcome deleterious side effects to establish LXR as new pharmacological targets.
authors.affiliation: Clermont Université, Université Blaise Pascal, Génétique Reproduction et Développement, BP 10448, F-63000 Clermont-Ferrand, France.
authors.forename: Emilie
authors.initials: E
authors.lastname: Viennois
authors.forename: Aurélien J C
authors.initials: AJ
authors.lastname: Pommier
authors.forename: Kévin
authors.initials: K
authors.lastname: Mouzat
authors.forename: Abdelkader
authors.initials: A
authors.lastname: Oumeddour
authors.forename: Fatim-Zohra
authors.initials: FZ
authors.lastname: El Hajjaji
authors.forename: Julie
authors.initials: J
authors.lastname: Dufour
authors.forename: Françoise
authors.initials: F
authors.lastname: Caira
authors.forename: David H
authors.initials: DH
authors.lastname: Volle
authors.forename: Silvère
authors.initials: S
authors.lastname: Baron
authors.forename: Jean-Marc A
authors.initials: JM
authors.lastname: Lobaccaro
mesh_terms: D000544:Alzheimer Disease / Q000188:drug therapy; D000818:Animals; D050197:Atherosclerosis / Q000188:drug therapy; D002784:Cholesterol / Q000097:blood / Q000378:metabolism*; D003920:Diabetes Mellitus / Q000188:drug therapy; D005260:Female; D006801:Humans; D008024:Ligands; D000071518:Liver X Receptors; D008297:Male; D051379:Mice; D058990:Molecular Targeted Therapy; D009369:Neoplasms / Q000188:drug therapy; D057093:Orphan Nuclear Receptors / Q000819:agonists / Q000037:antagonists & inhibitors / Q000737:chemistry / Q000378:metabolism*; D020033:Protein Isoforms / Q000737:chemistry / Q000378:metabolism; D012098:Reproduction; D012871:Skin Diseases / Q000188:drug therapy
chemical_list: D008024:Ligands; D000071518:Liver X Receptors; D057093:Orphan Nuclear Receptors; D020033:Protein Isoforms; D002784:Cholesterol