Abstract
Over the past years, an increasing amount of evidence has emerged in support of the kynurenine pathway’s (KP) pivotal role in the pathogenesis of several neurodegenerative, psychiatric, vascular and autoimmune diseases. Different neuroactive metabolites of the KP are known to exert opposite effects on neurons, some being neuroprotective (e.g., picolinic acid, kynurenic acid, and the cofactor nicotinamide adenine dinucleotide), while others are toxic to neurons (e.g., 3-hydroxykynurenine, quinolinic acid). Not only the alterations in the levels of the metabolites but also disturbances in their ratio (quinolinic acid/kynurenic acid) have been reported in several diseases. In addition to the metabolites, the enzymes participating in the KP have been unearthed to be involved in modulation of the immune system, the energetic upkeep of neurons and have been shown to influence redox processes and inflammatory cascades, revealing a sophisticated, intertwined system. This review considers various methods through which enzymes and metabolites of the kynurenine pathway influence the immune system, the roles they play in the pathogenesis of neuroinflammatory diseases based on current evidence with a focus on their involvement in multiple sclerosis, as well as therapeutic approaches.
Highlights
Even though kynurenic acid was discovered roughly 170 years ago, it was not until the 1970s and1980s that the kynurenine pathway (KP) sparked substantial interest among neuroscientists
In the early days of kynurenine research, the belief held for a long time that the main purpose of the KP is solely the production of nicotinamide adenine dinucleotide (NAD+ ), a coenzyme already known to be a pivotal molecule in a vast amount of vital biochemical processes including, but not limited to being a key component in several redox reactions and being vital to mitochondrial function [3]
We aim to summarize the mechanism of action and effect on the immune system and potential neuroprotective Laquinimod
Summary
Even though kynurenic acid was discovered roughly 170 years ago, it was not until the 1970s and. 1980s that the kynurenine pathway (KP) sparked substantial interest among neuroscientists This was due to the discovery that the two major products of the pathway, kynurenic acid (KYNA) and quinolinic acid (QUIN), possess significant, yet opposing effects on various neuronal cells and physiological processes [1]. Significant attention has been directed to the enzymes and metabolites of the KP, after the discovery that an alteration can be found in the metabolite levels but in the activity of the enzymes producing them as well in numerous disorders. In this review, following a concise introduction about the KP and its two most well-defined neuroactive metabolites, we aim to bring together recent evidence of their diverse effect on immunoregulatory mechanisms and their involvement in MS with a focus on a potential future therapeutic approach
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