ArticleNeurology(R) neuroimmunology & neuroinflammation2025
Dysregulation of the Kynurenine Pathway in Relapsing Remitting Multiple Sclerosis and Its Correlations With Progressive Neurodegeneration.
Article in Neurology(R) neuroimmunology & neuroinflammation, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers, 1 of them a synthesis that pooled it.
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Who cites it
11 citing papers in PubMed, 1 synthesis or guideline pooled it.
- Metabolomics in Multiple Sclerosis: Advances, Challenges, and Clinical Perspectives-A Systematic Review.International journal of molecular sciences · 2025Pooled it
- Sex-Specific Differences in Amino Acids and Neurotransmitters in Multiple Sclerosis Patients Compared to Non-Neuroinflammatory Controls: A Retrospective Case-Control Study.Neurochemical research · 2026Article
- Metabolic pathways linked to sarcopenia in the Bushehr Elderly Health Program: kynurenine, nicotinamide, B-vitamins, and sulfur amino acids.BMC geriatrics · 2026Article
- Central and Peripheral Characterization of Key Kynurenine Pathway Metabolites in Mexican Patients with Multiple Sclerosis: An Exploratory Study.Pharmaceuticals (Basel, Switzerland) · 2026Article
- CAR Treg therapies for neurodegenerative diseases.iScience · 2026Review
- Degradation of the Molecular Basis of Life During the Aging Process.International journal of molecular sciences · 2026Review
- Persons With Multiple Sclerosis Reveal Distinct Kynurenine Pathway Metabolite Patterns: A Multinational Cross-Sectional Study.Neurology(R) neuroimmunology & neuroinflammation · 2025Article
- Kynurenine Pathway Modulation by Exercise in Multiple Sclerosis: Implications for Neuroprotection and Inflammation.Cellular and molecular neurobiology · 2025Review
- Kynurenines and Mitochondrial Disturbances in Multiple Sclerosis.International journal of molecular sciences · 2025Review
- Glutamate-Based Therapeutic Strategies for Schizophrenia: Emerging Approaches Beyond Dopamine.International journal of molecular sciences · 2025Review
- Tryptophan pathway profiling in multiple sclerosis patients treated with ocrelizumab.Frontiers in immunology · 2025Article
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9 authors.
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No grant is acknowledged in the PubMed record.
Abstract
BACKGROUND AND
objectivesDespite the absence of acute lesion activity in multiple sclerosis (MS), chronic neurodegeneration continues to progress, and a potential underlying mechanism could be the kynurenine pathway (KP). Prolonged activation of the KP from chronic inflammation is known to exacerbate the progression of neurodegenerative diseases through the production of neurotoxic metabolites. Among the 8 KP metabolites, six of them, namely kynurenine (KYN), 3-hydroxylkynurenine (3HK), anthranilic acid (AA), kynurenic acid (KYNA), and quinolinic acid (QUIN), have been associated with neurodegeneration.
methodsTo gain insights into the links between the KP and neurodegeneration in MS, we investigated the KP metabolomics profile of relapsing remitting MS (RRMS) patients and their correlation with parameters of neurodegeneration in brain and retinal. Outpatients with a clinical diagnosis of RRMS (n = 98) or age-matched and sex-matched healthy controls (n = 39) were included. MS participants undertook yearly evaluation of MRI and optical coherence tomography scan to evaluate neuroaxonal loss. Blood samples were collected at the baseline from all participants for the biochemical analysis of KP metabolites.
resultsWe identified increased plasma levels of AA and 3HAA in the MS group, indicating an anti-inflammatory response alongside active neurodegeneration. By contrast, plasma levels of KYNA and 3HK were lower in the MS group than in healthy controls. Our analysis revealed a higher KYN:tryptophan (TRP) and QUIN:KYNA ratios in the MS cohort, suggesting activation of the pathway toward the production of neurotoxic QUIN. Another important finding was that KP metabolites were correlated with measures of axonal degeneration in patients with MS. Notably, central brain atrophy positively correlated with the TRP levels, but negatively correlated with KYN and level KYN:TRP ratio. Finally, the choroid plexus volume was inversely correlated with KYNA plasma levels. DISCUSSION: These findings highlight changes in the biosynthesis of KP during the progression of RRMS and its correlation with axonal loss. This study underscores the potential of targeting the KP in developing novel treatments for neuroaxonal damage in MS and warrants future research in greater depth.
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