title: Network of nuclear receptor ligands in multiple sclerosis: Common pathways and interactions of sex-steroids, corticosteroids and vitamin D3-derived molecules.
abstract: Sex-steroids, corticosteroids and vitamin D3-derived molecules have all been subject to experimental studies and clinical trials in a plethora of autoimmune diseases. These molecules are all derived from cholesterol metabolites and are ligands for nuclear receptors. Ligation of these receptors results in direct regulation of multiple gene transcription involved in general homeostatic and adaptation networks, including the immune system. Indeed, the distinct ligands affect the function of both myeloid and lymphoid cells, eventually resulting in a less pro-inflammatory immune response which is considered beneficial in autoimmune diseases. Next to the immune system, also the central nervous system is prone to regulation by these nuclear receptor ligands. Understanding of the intricate interactions between sex-steroids, corticosteroids and vitamin D3 metabolites, on the one hand, and the immune and central nervous system, on the other hand, may reveal novel approaches to utilize these nuclear receptor ligands to full extent as putative treatments in multiple sclerosis, the prototypic immune-driven disease of the central nervous system.
authors.affiliation: School for Mental Health and Neuroscience, Maastricht University Medical Center, Maastricht, The Netherlands; Academic MS Center Limburg, Zuyderland Medical Center, Sittard, The Netherlands.
authors.forename: Linda
authors.initials: L
authors.lastname: Rolf
authors.affiliation: Central Diagnostic Laboratory, Maastricht University Medical Center, Maastricht, The Netherlands.
authors.forename: Jan
authors.initials: J
authors.lastname: Damoiseaux
authors.affiliation: School for Mental Health and Neuroscience, Maastricht University Medical Center, Maastricht, The Netherlands; Academic MS Center Limburg, Zuyderland Medical Center, Sittard, The Netherlands.
authors.forename: Raymond
authors.initials: R
authors.lastname: Hupperts
authors.affiliation: Neuroimmunology Research Group, Netherlands Institute for Neuroscience, Amsterdam, The Netherlands.
authors.forename: Inge
authors.initials: I
authors.lastname: Huitinga
authors.affiliation: Academic MS Center Limburg, Zuyderland Medical Center, Sittard, The Netherlands; MS Center CWZ, Department of Neurology, Canisius Wilhelmina Hospital, Nijmegen, The Netherlands. Electronic address: smolders@gmail.com.
authors.forename: Joost
authors.initials: J
authors.lastname: Smolders
mesh_terms: D000305:Adrenal Cortex Hormones / Q000502:physiology*; D000818:Animals; D002490:Central Nervous System / Q000378:metabolism; D002762:Cholecalciferol / Q000502:physiology*; D012739:Gonadal Steroid Hormones / Q000502:physiology*; D006801:Humans; D008024:Ligands; D053858:Metabolic Networks and Pathways; D009103:Multiple Sclerosis / Q000276:immunology / Q000378:metabolism*; D018160:Receptors, Cytoplasmic and Nuclear / Q000502:physiology*
chemical_list: D000305:Adrenal Cortex Hormones; D012739:Gonadal Steroid Hormones; D008024:Ligands; D018160:Receptors, Cytoplasmic and Nuclear; D002762:Cholecalciferol
keywords: 1,25-Dihydroxyvitamin D; Corticosteroids; Cortisol; Estrogen; Glucocorticoids; Multiple sclerosis; Nuclear receptor ligands; Progesterone; Sex-steroids; T cells; Testosterone; Vitamin D