Liver X receptor and farnesoid X receptor as therapeutic targets.
Despite the success of existing therapies, new therapies targeted toward dyslipidemia are still needed. Liver X receptor (LXR) and farnesoid X receptor (FXR) represent 2 very different attractive targets for new therapeutic development. LXR is a nuclear receptor that primarily acts to rid cells and the body of excess cholesterol. LXR agonists have been shown to reduce atherosclerosis in animals and are therefore of great interest as a therapeutic approach. Despite some increases in hepatic fat and low-density lipoprotein (LDL) cholesterol in preclinical models, LXR remains an important new target. FXR is a nuclear receptor that primarily acts to protect hepatocytes against the effects of elevated bile acids. FXR agonists also have triglyceride-lowering properties and could be useful in treating certain types of dyslipidemia. FXR modulators or antagonists could potentially lower LDL cholesterol levels and even modulate high-density lipoprotein metabolism. FXR is a complicated but fascinating target for the development of new therapeutic approaches.
University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania 19104-6160, USA. rader@mail.med.upenn.edu
Daniel J
DJ
Rader
D000818:Animals; D050197:Atherosclerosis / Q000188:drug therapy* / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000819:agonists* / Q000187:drug effects; D015195:Drug Design; D050171:Dyslipidemias / Q000188:drug therapy* / Q000378:metabolism; D006801:Humans; D000960:Hypolipidemic Agents / Q000494:pharmacology*; D000071518:Liver X Receptors; D057093:Orphan Nuclear Receptors; D018160:Receptors, Cytoplasmic and Nuclear / Q000819:agonists* / Q000187:drug effects; D014157:Transcription Factors / Q000819:agonists* / Q000187:drug effects; D000099150:Receptor, Farnesoid X-Activated
D004268:DNA-Binding Proteins; D000960:Hypolipidemic Agents; D000071518:Liver X Receptors; D057093:Orphan Nuclear Receptors; D018160:Receptors, Cytoplasmic and Nuclear; D014157:Transcription Factors; D000099150:Receptor, Farnesoid X-Activated