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Download fileKynurenine pathway metabolomics predicts and provides mechanistic insight into multiple sclerosis progression
journal contribution
posted on 2023-05-19, 03:17 authored by Lim, CK, Bilgin, A, Lovejoy, DB, Tan, V, Bustamante, S, Bruce TaylorBruce Taylor, Bessede, A, Brew, BJ, Guillemin, GJActivation of the kynurenine pathway (KP) of tryptophan metabolism results from chronic inflammation and is known to exacerbate progression of neurodegenerative disease. To gain insights into the links between inflammation, the KP and multiple sclerosis (MS) pathogenesis, we investigated the KP metabolomics profile of MS patients. Most significantly, we found aberrant levels of two key KP metabolites, kynurenic acid (KA) and quinolinic acid (QA). The balance between these metabolites is important as it determines overall excitotoxic activity at the N-methyl-D-Aspartate (NMDA) receptor. We also identified that serum KP metabolic signatures in patients can discriminate clinical MS subtypes with high sensitivity and specificity. A C5.0 Decision Tree classification model discriminated the clinical subtypes of MS with a sensitivity of 91%. After validation in another independent cohort, sensitivity was maintained at 85%. Collectively, our studies suggest that abnormalities in the KP may be associated with the switch from early-mild stage MS to debilitating progressive forms of MS and that analysis of KP metabolites in MS patient serum may have application as MS disease biomarkers.
History
Publication title
Scientific ReportsVolume
7Article number
41473Number
41473Pagination
1-9ISSN
2045-2322Department/School
Menzies Institute for Medical ResearchPublisher
Nature Publishing GroupPlace of publication
United KingdomRights statement
© The Author(s) 2017 Licensed under Creative Commons Attribution 4.0 International (CC BY 4.0) https://creativecommons.org/licenses/by/4.0/Repository Status
- Open