title: Multiple sclerosis: the role of melatonin and N-acetylserotonin.
abstract: Multiple sclerosis (MS) is an immune mediated disorder that is under intensive investigation in an attempt to improve on available treatments. Many of the changes occurring in MS, including increased mitochondrial dysfunction, pain reporting and depression may be partly mediated by increased indoleamine 2,3-dioxygenase, which drives tryptophan to the production of neuroregulatory tryptophan catabolites and away from serotonin, N-acetylserotonin and melatonin production. The consequences of decreased melatonin have classically been attributed to circadian changes following its release from the pineal gland. However, recent data shows that melatonin may be produced by all mitochondria containing cells to some degree, including astrocytes and immune cells, thereby providing another important MS treatment target. As well as being a powerful antioxidant, anti-inflammatory and antinociceptive, melatonin improves mitochondrial functioning, partly via increased oxidative phosphorylation. Melatonin also inhibits demyelination and increases remyelination, suggesting that its local regulation in white matter astrocytes by serotonin availability and apolipoprotein E4, among other potential factors, will be important in the etiology, course and treatment of MS. Here we review the role of local melatonin and its precursors, N-acetylserotonin and serotonin, in MS.
authors: CRC Scotland & London, Eccleston Square, London, UK. Electronic address: anderson.george@rocketmail.com.
authors: George
authors: G
authors: Anderson
authors: Mayo Clinic, Rochester, MN, USA.
authors: Moses
authors: M
authors: Rodriguez
mesh_terms: D000068876:Fingolimod Hydrochloride / Q000627:therapeutic use; D000068717:Glatiramer Acetate / Q000627:therapeutic use; D006801:Humans; D007155:Immunologic Factors / Q000627:therapeutic use; D007166:Immunosuppressive Agents / Q000627:therapeutic use; D016899:Interferon-beta / Q000627:therapeutic use; D018020:Lithium Compounds / Q000627:therapeutic use; D008550:Melatonin / Q000502:physiology*; D009103:Multiple Sclerosis / Q000188:drug therapy / Q000209:etiology*; D018697:Nootropic Agents / Q000627:therapeutic use; D012701:Serotonin / Q000031:analogs & derivatives* / Q000502:physiology; D014635:Valproic Acid / Q000627:therapeutic use
chemical_list: D007155:Immunologic Factors; D007166:Immunosuppressive Agents; D018020:Lithium Compounds; D018697:Nootropic Agents; D012701:Serotonin; D000068717:Glatiramer Acetate; D014635:Valproic Acid; D016899:Interferon-beta; D000068876:Fingolimod Hydrochloride; D008550:Melatonin; C006389:N-acetylserotonin
keywords: Depression; Melatonin; Mitochondria; Multiple sclerosis; N-Acetylserotonin; Remyelination