Oxysterols receptor LXR-alpha
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. 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. Polymorphisms are also linked to increased susceptibility to systemic lupus erythematosus or decreased susceptibility to Alzheimer's disease. Oxysterols receptor LXR-alpha is the master regulator of cholesterol homeostasis in macrophages. It is a potential therapeutic target for the treatment of atherosclerosis, although with all these other disease associations therapeutic development may prove challenging.
- ↑ Maqdasy S, Trousson A, Tauveron I, Volle DH, Baron S, Lobaccaro JM. Once and for all, LXRα and LXRβ are gatekeepers of the endocrine system. Molecular aspects of medicine. 2016 Jun; 49:31-46.(Link to article – subscription may be required.)
- ↑ Wang et al., 2016, Neuron 90, 948–954 June 1, 2016 http://dx.doi.org/10.1016/j.neuron.2016.04.039
- ↑ Jeon JY, Nam JY, Kim HA, Park YB, Bae SC, Suh CH. Liver X receptors alpha gene (NR1H3) promoter polymorphisms are associated with systemic lupus erythematosus in Koreans. Arthritis research & therapy. 2014; 16(3):R112.(Epub) (Link to article – subscription may be required.)
- ↑ Natunen T, Martiskainen H, Sarajärvi T, Helisalmi S, Pursiheimo JP, Viswanathan J, Laitinen M, Mäkinen P, Kauppinen T, Rauramaa T, Leinonen V, Alafuzoff I, Haapasalo A, Soininen H, Hiltunen M. Effects of NR1H3 genetic variation on the expression of liver X receptor α and the progression of Alzheimer's disease. PloS one. 2013; 8(11):e80700.(Epub) (Link to article – subscription may be required.)
- ↑ Whitney KD, Watson MA, Goodwin B, Galardi CM, Maglich JM, Wilson JG, Willson TM, Collins JL, Kliewer SA. Liver X receptor (LXR) regulation of the LXRalpha gene in human macrophages. The Journal of biological chemistry. 2001 Nov 23; 276(47):43509-15.(Link to article – subscription may be required.)