eCite Digital Repository

Kynurenine pathway metabolomics predicts and provides mechanistic insight into multiple sclerosis progression

Citation

Lim, CK and Bilgin, A and Lovejoy, DB and Tan, V and Bustamante, S and Taylor, BV and Bessede, A and Brew, BJ and Guillemin, GJ, Kynurenine pathway metabolomics predicts and provides mechanistic insight into multiple sclerosis progression, Scientific Reports, 7 Article 41473. ISSN 2045-2322 (2017) [Refereed Article]


Preview
PDF
370Kb
  

Copyright Statement

The Author(s) 2017 Licensed under Creative Commons Attribution 4.0 International (CC BY 4.0) https://creativecommons.org/licenses/by/4.0/

DOI: doi:10.1038/srep41473

Abstract

Activation 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.

Item Details

Item Type:Refereed Article
Research Division:Medical and Health Sciences
Research Group:Neurosciences
Research Field:Central Nervous System
Objective Division:Health
Objective Group:Clinical Health (Organs, Diseases and Abnormal Conditions)
Objective Field:Nervous System and Disorders
Author:Taylor, BV (Professor Bruce Taylor)
ID Code:115409
Year Published:2017
Web of Science® Times Cited:3
Deposited By:Menzies Institute for Medical Research
Deposited On:2017-03-22
Last Modified:2017-04-03
Downloads:4 View Download Statistics

Repository Staff Only: item control page