Estrogen Receptor Beta And Liver X Receptor Beta: Biology And Therapeutic Potential In Cns Diseases

In the last decade of the twentieth century, two nuclear receptors were discovered in our laboratory and, very surprisingly, were found to have key roles in the central nervous system. These receptors have provided some novel insights into the etiology and progression of neurodegenerative diseases and anxiety disorders. The two receptors are estrogen receptor beta (ER beta) and liver X receptor beta (LXR beta). Both ER beta and LXR beta have potent anti-inflammatory activities and, in addition, LXR beta is involved in the genesis of dopaminergic neurons during development and protection of these neurons against neurodegeneration in adult life. ER beta is involved in migration of cortical neurons and calretinin-positive GABAergic interneurons during development and maintenance of serotonergic neurons in adults. Both receptors are present in magnocellular neurons of the hypothalamic preoptic area including those expressing vasopressin and oxytocin. As both ER beta and LXR beta are ligand-activated transcription factors, their ligands hold great potential in the treatment of diseases of the CNS.