TY - JOUR
T1 - Liver X receptor biology and pharmacology
T2 - New pathways, challenges and opportunities
AU - Jakobsson, Tomas
AU - Treuter, Eckardt
AU - Gustafsson, Jan Åke
AU - Steffensen, Knut R.
N1 - Funding Information:
This study was supported by grants from the Center for Biosciences (E.T., J-Å.G), the Novo Nordisk Foundation (E.T.), the Swedish Research Council (E.T., J-Å.G., K.R.S.), the Welch Foundation (J-Å.G.) and the Emerging Technology Fund of Texas (J-Å.G.). K.R.S. holds a research assistant professorship from the Swedish Research Council (contract no. 522-2008-3745).
PY - 2012/7
Y1 - 2012/7
N2 - Nuclear receptors (NRs) are master regulators of transcriptional programs that integrate the homeostatic control of almost all biological processes. Their direct mode of ligand regulation and genome interaction is at the core of modern pharmacology. The two liver X receptors LXRα and LXRβ are among the emerging newer drug targets within the NR family. LXRs are best known as nuclear oxysterol receptors and physiological regulators of lipid and cholesterol metabolism that also act in an anti-inflammatory way. Because LXRs control diverse pathways in development, reproduction, metabolism, immunity and inflammation, they have potential as therapeutic targets for diseases as diverse as lipid disorders, atherosclerosis, chronic inflammation, autoimmunity, cancer and neurodegenerative diseases. Recent insights into LXR signaling suggest future targeting strategies aiming at increasing LXR subtype and pathway selectivity. This review discusses the current status of our understanding of LXR biology and pharmacology, with an emphasis on the molecular aspects of LXR signaling that constitute the potential of LXRs as drug targets.
AB - Nuclear receptors (NRs) are master regulators of transcriptional programs that integrate the homeostatic control of almost all biological processes. Their direct mode of ligand regulation and genome interaction is at the core of modern pharmacology. The two liver X receptors LXRα and LXRβ are among the emerging newer drug targets within the NR family. LXRs are best known as nuclear oxysterol receptors and physiological regulators of lipid and cholesterol metabolism that also act in an anti-inflammatory way. Because LXRs control diverse pathways in development, reproduction, metabolism, immunity and inflammation, they have potential as therapeutic targets for diseases as diverse as lipid disorders, atherosclerosis, chronic inflammation, autoimmunity, cancer and neurodegenerative diseases. Recent insights into LXR signaling suggest future targeting strategies aiming at increasing LXR subtype and pathway selectivity. This review discusses the current status of our understanding of LXR biology and pharmacology, with an emphasis on the molecular aspects of LXR signaling that constitute the potential of LXRs as drug targets.
UR - http://www.scopus.com/inward/record.url?scp=84862687669&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84862687669&partnerID=8YFLogxK
U2 - 10.1016/j.tips.2012.03.013
DO - 10.1016/j.tips.2012.03.013
M3 - Review article
C2 - 22541735
AN - SCOPUS:84862687669
SN - 0165-6147
VL - 33
SP - 394
EP - 404
JO - Trends in Pharmacological Sciences
JF - Trends in Pharmacological Sciences
IS - 7
ER -