Oxysterols receptor LXR-alpha

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The NR1H3 gene at 11p11.2 codes for the 447 amino acid peptide oxysterols receptor LXR-alpha, a liver X receptor. This is a nuclear receptor whose transcriptional activity is regulated by oxysterols, the oxidized forms of cholesterol. There are three isoforms formed by alternative splicing. This is a cholesterol sensor highly expressed in the liver, adipose, kidney, adrenal tissues, and macrophages. As well as regulating cholesterol and fatty acid homeostasis it has other physiological functions including glucose homeostasis, immunological, and neuroprotective[1]. Dysfunction of the gene in animal models decreases myelin production which is not inconsistent with mutations of the gene being linked in man to increased risk of multiple sclerosis[2]. Polymorphisms are also linked to increased susceptibility to systemic lupus erythematosus[3] or decreased susceptibility to Alzheimer's disease[4]. Oxysterols receptor LXR-alpha is the master regulator of cholesterol homeostasis in macrophages. It is a potential therapeutic target for the treatment of atherosclerosis[5], although with all these other disease associations therapeutic development may prove challenging.