Estrogen receptor β and Liver X receptor β: biology and therapeutic potential in CNS diseases

• Published in: Molecular psychiatry Vol. 20; no. 1; pp. 18 - 22
• Main Authors: Warner, M, Gustafsson, J-A
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 2015; Nature Publishing Group
• Subjects: 631/378/340; 692/420; 692/699/375/365; 692/699/476; Animals; Anxiety; Behavioral Sciences; Biological Psychology; Calretinin; Care and treatment; Cell Movement - drug effects; Cell Movement - physiology; Central nervous system; Central nervous system diseases; Central Nervous System Diseases - genetics; Central Nervous System Diseases - metabolism; Central Nervous System Diseases - therapy; Cerebral Cortex - pathology; Development and progression; Dopamine receptors; Estrogen; Estrogen Receptor beta - agonists; Estrogen Receptor beta - genetics; Estrogen Receptor beta - metabolism; Etiology; expert-review; Humans; Hypothalamus; Inflammation; Interneurons; Ligands; Liver; Liver X Receptors; Magnocellular neurons; Medical treatment; Medicin och hälsovetenskap; Medicine; Medicine & Public Health; Neurodegeneration; Neurodegenerative diseases; Neurons; Neurons - physiology; Neurosciences; Nuclear receptors; Orphan Nuclear Receptors - agonists; Orphan Nuclear Receptors - genetics; Orphan Nuclear Receptors - metabolism; Oxytocin; Pharmacotherapy; Physiological aspects; Preoptic area; Psychiatry; Receptors; Serotonin; Transcription factors; Vasopressin
• ISSN: 1359-4184; 1476-5578; 1476-5578
• DOI: 10.1038/mp.2014.23

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 (ERβ) and liver X receptor beta (LXRβ). Both ERβ and LXRβ have potent anti-inflammatory activities and, in addition, LXRβ is involved in the genesis of dopaminergic neurons during development and protection of these neurons against neurodegeneration in adult life. ERβ 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 ERβ and LXRβ are ligand-activated transcription factors, their ligands hold great potential in the treatment of diseases of the CNS.