Liver X receptors as potential therapeutic targets for multiple diseases.
Liver X receptor alpha (LXRalpha) and liver X receptor beta(LXRbeta are oxysterol receptors that regulate multiple target genes involved in cholesterol homeostasis. Recent studies also suggest that the pair of receptors may also be involved in glucose metabolism, inflammation and Alzheimer's disease by regulating critical molecules involved in these pathophysiological processes. Although the prototypic LXR agonists induce liver triglyceride accumulation by regulating the hepatic lipogenesis pathway, it is hoped that a subtype-specific agonist or selective modulators would provide the desired cardioprotection and other benefits without the undesirable concomitant induction of lipogenesis. This review intends to summarize the most recent progress in the field and provide an assessment of LXRs as potential therapeutic targets.
Cao
Guoqing
G
Division of Cardiovascular Discovery, Lilly Research Laboratories, Eli Lilly & Company, Indianapolis, Indiana 46285, USA. Guoqing_Cao@lilly.com
Liang
Yu
Y
Jiang
Xian-Cheng
XC
Eacho
Patrick I
PI
D000544:Alzheimer Disease / Q000503:physiopathology / Q000517:prevention & control; D000818:Animals; D001161:Arteriosclerosis / Q000503:physiopathology / Q000517:prevention & control; D001786:Blood Glucose / Q000378:metabolism; D002784:Cholesterol / Q000502:physiology; D004268:DNA-Binding Proteins; D005227:Fatty Acids / Q000378:metabolism; D006706:Homeostasis; D007249:Inflammation / Q000378:metabolism / Q000517:prevention & control; D008099:Liver / Q000378:metabolism*; D000071518:Liver X Receptors; D051379:Mice; D057093:Orphan Nuclear Receptors; D051381:Rats; D018160:Receptors, Cytoplasmic and Nuclear / Q000819:agonists / Q000378:metabolism*
D001786:Blood Glucose; D004268:DNA-Binding Proteins; D005227:Fatty Acids; D000071518:Liver X Receptors; C000605214:Nr1h3 protein, mouse; C000605215:Nr1h3 protein, rat; D057093:Orphan Nuclear Receptors; D018160:Receptors, Cytoplasmic and Nuclear; D002784:Cholesterol