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Dynamic changes in kynurenine pathway metabolites in multiple sclerosis: A systematic review
BACKGROUND: Multiple sclerosis (MS) is a debilitating neurodegenerative disorder characterized by axonal damage, demyelination, and perivascular inflammatory lesions in the white matter of the central nervous system (CNS). Kynurenine pathway (KP), which is the major route of tryptophan (TRP) metabol...
Autores principales: | , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Frontiers Media S.A.
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9680557/ https://www.ncbi.nlm.nih.gov/pubmed/36426364 http://dx.doi.org/10.3389/fimmu.2022.1013784 |
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author | Fathi, Mobina Vakili, Kimia Yaghoobpoor, Shirin Tavasol, Arian Jazi, Kimia Mohamadkhani, Ashraf Klegeris, Andis McElhinney, Alyssa Mafi, Zahedeh Hajiesmaeili, Mohammadreza Sayehmiri, Fatemeh |
author_facet | Fathi, Mobina Vakili, Kimia Yaghoobpoor, Shirin Tavasol, Arian Jazi, Kimia Mohamadkhani, Ashraf Klegeris, Andis McElhinney, Alyssa Mafi, Zahedeh Hajiesmaeili, Mohammadreza Sayehmiri, Fatemeh |
author_sort | Fathi, Mobina |
collection | PubMed |
description | BACKGROUND: Multiple sclerosis (MS) is a debilitating neurodegenerative disorder characterized by axonal damage, demyelination, and perivascular inflammatory lesions in the white matter of the central nervous system (CNS). Kynurenine pathway (KP), which is the major route of tryptophan (TRP) metabolism, generates a variety of neurotoxic as well as neuroprotective compounds, affecting MS pathology and the severity of impairments. Alterations in KP have been described not only in MS, but also in various psychiatric and neurodegenerative diseases. The purpose of this systematic review is to investigate the previously reported dysregulation of KP and differences in its metabolites and enzymes in patients with MS compared to healthy control subjects. METHOD: Electronic databases of PubMed, Scopus, Cochrane Database of Systematic Reviews, and Web of Science were searched to identify studies measuring concentrations of KP metabolites and enzymes in MS patients and control subjects. The following metabolites and enzymes implicated in the KP were investigated: TRP, kynurenine (KYN), kynurenic acid (KYNA), quinolinic acid (QUIN), picolinic acid (PIC), hydroxyindoleacetic acid (HIAA), indoleamine 2,3-dioxygenase (IDO), kynurenine aminotransferase (KAT), and their related ratios. RESULT: Ten studies were included in our systematic review. Our review demonstrates that IDO expression is reduced in the peripheral blood mononuclear cells (PBMCs) of MS patients compared to healthy controls. Also, increased levels of QUIN and QUIN/KYNA in the serum and cerebrospinal fluid (CSF) of MS patients is observed. Differences in levels of other metabolites and enzymes of KP are also reported in some of the reviewed studies, however there are discrepancies among the included reports. CONCLUSION: The results of this investigation suggest a possible connection between alterations in the levels of KP metabolite or enzymes and MS. QUIN levels in CSF were higher in MS patients than in healthy controls, suggesting that QUIN may be involved in the pathogenesis of MS. The data indicate that differences in the serum/blood or CSF levels of certain KP metabolites and enzymes could potentially be used to differentiate between MS patients and control subjects. |
format | Online Article Text |
id | pubmed-9680557 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-96805572022-11-23 Dynamic changes in kynurenine pathway metabolites in multiple sclerosis: A systematic review Fathi, Mobina Vakili, Kimia Yaghoobpoor, Shirin Tavasol, Arian Jazi, Kimia Mohamadkhani, Ashraf Klegeris, Andis McElhinney, Alyssa Mafi, Zahedeh Hajiesmaeili, Mohammadreza Sayehmiri, Fatemeh Front Immunol Immunology BACKGROUND: Multiple sclerosis (MS) is a debilitating neurodegenerative disorder characterized by axonal damage, demyelination, and perivascular inflammatory lesions in the white matter of the central nervous system (CNS). Kynurenine pathway (KP), which is the major route of tryptophan (TRP) metabolism, generates a variety of neurotoxic as well as neuroprotective compounds, affecting MS pathology and the severity of impairments. Alterations in KP have been described not only in MS, but also in various psychiatric and neurodegenerative diseases. The purpose of this systematic review is to investigate the previously reported dysregulation of KP and differences in its metabolites and enzymes in patients with MS compared to healthy control subjects. METHOD: Electronic databases of PubMed, Scopus, Cochrane Database of Systematic Reviews, and Web of Science were searched to identify studies measuring concentrations of KP metabolites and enzymes in MS patients and control subjects. The following metabolites and enzymes implicated in the KP were investigated: TRP, kynurenine (KYN), kynurenic acid (KYNA), quinolinic acid (QUIN), picolinic acid (PIC), hydroxyindoleacetic acid (HIAA), indoleamine 2,3-dioxygenase (IDO), kynurenine aminotransferase (KAT), and their related ratios. RESULT: Ten studies were included in our systematic review. Our review demonstrates that IDO expression is reduced in the peripheral blood mononuclear cells (PBMCs) of MS patients compared to healthy controls. Also, increased levels of QUIN and QUIN/KYNA in the serum and cerebrospinal fluid (CSF) of MS patients is observed. Differences in levels of other metabolites and enzymes of KP are also reported in some of the reviewed studies, however there are discrepancies among the included reports. CONCLUSION: The results of this investigation suggest a possible connection between alterations in the levels of KP metabolite or enzymes and MS. QUIN levels in CSF were higher in MS patients than in healthy controls, suggesting that QUIN may be involved in the pathogenesis of MS. The data indicate that differences in the serum/blood or CSF levels of certain KP metabolites and enzymes could potentially be used to differentiate between MS patients and control subjects. Frontiers Media S.A. 2022-11-02 /pmc/articles/PMC9680557/ /pubmed/36426364 http://dx.doi.org/10.3389/fimmu.2022.1013784 Text en Copyright © 2022 Fathi, Vakili, Yaghoobpoor, Tavasol, Jazi, Mohamadkhani, Klegeris, McElhinney, Mafi, Hajiesmaeili and Sayehmiri https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. |
spellingShingle | Immunology Fathi, Mobina Vakili, Kimia Yaghoobpoor, Shirin Tavasol, Arian Jazi, Kimia Mohamadkhani, Ashraf Klegeris, Andis McElhinney, Alyssa Mafi, Zahedeh Hajiesmaeili, Mohammadreza Sayehmiri, Fatemeh Dynamic changes in kynurenine pathway metabolites in multiple sclerosis: A systematic review |
title | Dynamic changes in kynurenine pathway metabolites in multiple sclerosis: A systematic review |
title_full | Dynamic changes in kynurenine pathway metabolites in multiple sclerosis: A systematic review |
title_fullStr | Dynamic changes in kynurenine pathway metabolites in multiple sclerosis: A systematic review |
title_full_unstemmed | Dynamic changes in kynurenine pathway metabolites in multiple sclerosis: A systematic review |
title_short | Dynamic changes in kynurenine pathway metabolites in multiple sclerosis: A systematic review |
title_sort | dynamic changes in kynurenine pathway metabolites in multiple sclerosis: a systematic review |
topic | Immunology |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9680557/ https://www.ncbi.nlm.nih.gov/pubmed/36426364 http://dx.doi.org/10.3389/fimmu.2022.1013784 |
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