Dynamic changes in kynurenine pathway metabolites in multiple sclerosis: A systematic review
BackgroundMultiple 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) metabolis...
| Main Authors: | , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2022-11-01
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| Series: | Frontiers in Immunology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fimmu.2022.1013784/full |
| _version_ | 1797985143976099840 |
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| author | Mobina Fathi Kimia Vakili Shirin Yaghoobpoor Arian Tavasol Kimia Jazi Ashraf Mohamadkhani Andis Klegeris Alyssa McElhinney Zahedeh Mafi Mohammadreza Hajiesmaeili Fatemeh Sayehmiri |
| author_facet | Mobina Fathi Kimia Vakili Shirin Yaghoobpoor Arian Tavasol Kimia Jazi Ashraf Mohamadkhani Andis Klegeris Alyssa McElhinney Zahedeh Mafi Mohammadreza Hajiesmaeili Fatemeh Sayehmiri |
| author_sort | Mobina Fathi |
| collection | DOAJ |
| description | BackgroundMultiple 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.MethodElectronic 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.ResultTen 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.ConclusionThe 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. |
| first_indexed | 2024-04-11T07:13:57Z |
| format | Article |
| id | doaj.art-f2e3096d477642b4b11dfecc6a756380 |
| institution | Directory Open Access Journal |
| issn | 1664-3224 |
| language | English |
| last_indexed | 2024-04-11T07:13:57Z |
| publishDate | 2022-11-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Immunology |
| spelling | doaj.art-f2e3096d477642b4b11dfecc6a7563802022-12-22T04:38:04ZengFrontiers Media S.A.Frontiers in Immunology1664-32242022-11-011310.3389/fimmu.2022.10137841013784Dynamic changes in kynurenine pathway metabolites in multiple sclerosis: A systematic reviewMobina Fathi0Kimia Vakili1Shirin Yaghoobpoor2Arian Tavasol3Kimia Jazi4Ashraf Mohamadkhani5Andis Klegeris6Alyssa McElhinney7Zahedeh Mafi8Mohammadreza Hajiesmaeili9Fatemeh Sayehmiri10Student Research Committee, Faculty of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, IranStudent Research Committee, Faculty of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, IranStudent Research Committee, Faculty of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, IranStudent Research Committee, Faculty of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, IranFaculty of Medicine, Medical University of Qom, Qom, IranLiver and Pancreatobiliary Diseases Research Center, Digestive Disease Research Institute, Shariati Hospital, Tehran University of Medical Sciences, Tehran, IranDepartment of Biology, Faculty of Science, University of British Columbia, Kelowna, BC, CanadaDepartment of Biology, Faculty of Science, University of British Columbia, Kelowna, BC, CanadaFaculty of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, IranCritical Care Quality Improvement Research Center, Loghman Hakim Hospital, Shahid Beheshti University of Medical Sciences, Tehran, IranStudent Research Committee, Faculty of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, IranBackgroundMultiple 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.MethodElectronic 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.ResultTen 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.ConclusionThe 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.https://www.frontiersin.org/articles/10.3389/fimmu.2022.1013784/fullmultiple sclerosiskynurenine pathwaykynureninetryptophanpicolinic acidhydroxyindoleacetic acid |
| spellingShingle | Mobina Fathi Kimia Vakili Shirin Yaghoobpoor Arian Tavasol Kimia Jazi Ashraf Mohamadkhani Andis Klegeris Alyssa McElhinney Zahedeh Mafi Mohammadreza Hajiesmaeili Fatemeh Sayehmiri Dynamic changes in kynurenine pathway metabolites in multiple sclerosis: A systematic review Frontiers in Immunology multiple sclerosis kynurenine pathway kynurenine tryptophan picolinic acid hydroxyindoleacetic acid |
| 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 | multiple sclerosis kynurenine pathway kynurenine tryptophan picolinic acid hydroxyindoleacetic acid |
| url | https://www.frontiersin.org/articles/10.3389/fimmu.2022.1013784/full |
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