title: Kynurenine System and Multiple Sclerosis, Pathomechanism and Drug Targets with An Emphasis on Laquinimod.
abstract: Multiple sclerosis is a common chronic, disabling autoimmune neurological disease affecting mainly young adults. In its pathomechanism, neurodegenerative and acute inflammatory characteristics are both involved. Disease-modifying therapies aim to reduce relapse-rate and slow down the deterioration in neurological functions. The currently available therapies fail to exert neuroprotective effects and most of them are associated with potentially toxic side-effects, therefore, ongoing research aims to develop novel drug candidates to cover these therapeutic gaps. The kynurenine pathway has been implicated in both the physiological processes of the central nervous system and in the pathomechanism of several neurological disorders as well. Alterations of the kynurenine pathway metabolites have been detected in multiple sclerosis and a number of potential therapeutic targets related to this metabolic route have been already identified. Laquinimod is a quinoline carboxamide showing structural similarities with kynurenic acid, which proved to have beneficial effects on reduction of brain atrophy and disability progression. The kynurenine pathway is therefore a promising target for the development of future drugs for the treatment of autoimmune diseases such as multiple sclerosis.
authors.affiliation: University of Szeged, Department of Neurology, Semmelweis u. 6, H-6725, Szeged, Hungary.
authors.forename: Zsofia
authors.initials: Z
authors.lastname: Majlath
authors.affiliation: University of Szeged, Department of Neurology, Semmelweis u. 6, H-6725, Szeged, Hungary.
authors.forename: Adam
authors.initials: A
authors.lastname: Annus
authors.affiliation: University of Szeged, Department of Neurology, Semmelweis u. 6, H-6725, Szeged, Hungary.|MTA-SZTE Neuroscience Research Group of the Hungarian Academy of Sciences and University of Szeged, Semmelweis u. 6, H-6725 Szeged, Hungary.
authors.forename: Laszlo
authors.initials: L
authors.lastname: Vecsei
mesh_terms: D000818:Animals; D001921:Brain / Q000187:drug effects / Q000503:physiopathology; D018450:Disease Progression; D000076722:Drug Development / Q000379:methods; D006801:Humans; D007737:Kynurenine / Q000378:metabolism*; D058990:Molecular Targeted Therapy; D009103:Multiple Sclerosis / Q000188:drug therapy* / Q000503:physiopathology; D018696:Neuroprotective Agents / Q000494:pharmacology / Q000627:therapeutic use; D015363:Quinolones / Q000494:pharmacology / Q000627:therapeutic use*; D055815:Young Adult
chemical_list: D018696:Neuroprotective Agents; D015363:Quinolones; D007737:Kynurenine; C476223:laquinimod
keywords: Multiple sclerosis; kynurenine system; laquinimod; neuroinflammation; neuroprotection.