Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
5912831 | Multiple Sclerosis and Related Disorders | 2015 | 73 Pages |
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.
Keywords
MAOINASEAEIFN-γTrkBMecp2NK-1RPGC-1αS1PIDOSMaseT-helperTLRMTRLXRNF-κβ4HNEYY1AMKAFMKO&NSLIFAA-NATtryptophan catabolitesGSHMIRAHRnatural killerBDNFcAMPN-acetylserotoninRemyelinationCyclic adenosine monophosphateexperimental autoimmune encephalomyelitisapoapolipoproteinOxidative and nitrosative stressSphingosine-1-phosphatesphingomyelinasekynurenic acidDepressionIndoleamine 2, 3-dioxygenaseinterferon-gammainterleukintumor necrosis factor-alphaToll-like receptorFTORegulatory T cellsbrain derived neurotrophic factorTNF-αnuclear factor-kappa betaSubstance PMelatoninSelective serotonin reuptake inhibitormonoamine oxidase inhibitorSSRIMultiple sclerosisMitochondriaMicroRNABlood–brain barrier permeabilitynorepinephrineHiomtmethyl-CpG-binding protein 2Single nucleotide polymorphismSNPliver X receptorKYNAglatiramer acetateGlutathioneBeta2-adrenergic receptoraryl hydrocarbon receptorMelatonin receptorNeurokinin-1 receptorYin Yang 1
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Authors
George Anderson, Moses Rodriguez,