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.
Curr Drug Targets. 2018;19(7):805-814. doi: 10.2174/1389450117666161223125417.
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.
多发性硬化症是一种常见的慢性、致残性自身免疫性神经系统疾病，主要影响年轻人。在其发病机制中，神经退行性和急性炎症特征都有涉及。疾病修正疗法旨在降低复发率和减缓神经功能恶化。目前可用的治疗方法未能发挥神经保护作用，而且大多数都与潜在的毒性副作用相关，因此，正在进行的研究旨在开发新的药物候选物来填补这些治疗空白。犬尿氨酸途径不仅与中枢神经系统的生理过程有关，而且与几种神经紊乱的发病机制也有关。在多发性硬化症中已经检测到犬尿氨酸途径代谢物的改变，并且已经确定了与这种代谢途径相关的一些潜在治疗靶点。拉喹莫德是一种喹啉羧酰胺，与犬尿氨酸具有结构相似性，已被证明对减少脑萎缩和残疾进展有有益作用。因此，犬尿氨酸途径是开发治疗自身免疫性疾病（如多发性硬化症）的未来药物的有前途的靶点。
