{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T11:49:22Z","timestamp":1791287362477,"version":"4.1.0"},"reference-count":93,"publisher":"MDPI AG","issue":"11","license":[{"start":{"date-parts":[[2025,5,26]],"date-time":"2025-05-26T00:00:00Z","timestamp":1748217600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"National Research, Development, and Innovation Office","award":["NKFIHK138125"],"award-info":[{"award-number":["NKFIHK138125"]}]},{"name":"National Research, Development, and Innovation Office","award":["SZTE SZAOK-KKA No: 2022\/5S729"],"award-info":[{"award-number":["SZTE SZAOK-KKA No: 2022\/5S729"]}]},{"name":"HUN-REN Hungarian Research Network","award":["NKFIHK138125"],"award-info":[{"award-number":["NKFIHK138125"]}]},{"name":"HUN-REN Hungarian Research Network","award":["SZTE SZAOK-KKA No: 2022\/5S729"],"award-info":[{"award-number":["SZTE SZAOK-KKA No: 2022\/5S729"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Multiple sclerosis (MS) is a chronic autoimmune disease characterised by inflammation, demyelination, and neurodegeneration within the central nervous system. The pathogenesis of MS involves an immune-mediated attack on myelin and neurons, accompanied by blood\u2013brain barrier dysfunction and chronic CNS inflammation. Central to MS pathology is dysregulation of the kynurenine pathway, which metabolises tryptophan into neuroactive compounds. Kynurenine pathway (KP) activation, driven by inflammatory cytokines, leads to the production of both neuroprotective (e.g., kynurenic acid, KYNA) and neurotoxic (e.g., quinolinic acid, QUIN) metabolites. Imbalance between these metabolites, particularly increased QUIN production, exacerbates glutamate excitotoxicity, oxidative stress, and mitochondrial dysfunction, contributing to neuronal and oligodendrocyte damage. Mitochondrial dysfunction plays a critical role in the pathophysiology of MS, exacerbating neurodegeneration through impaired energy metabolism and oxidative stress. This review integrates the current understanding of KP dysregulation in multiple sclerosis across disease stages. In RRMS, heightened KP activity correlates with inflammation and neuroprotection attempts through increased KYNA production. In contrast, SPMS and PPMS are associated with a shift towards a more neurotoxic KP profile, marked by elevated QUIN levels and reduced KYNA, exacerbating neurodegeneration and disability progression. Understanding these mechanisms offers insights into potential biomarkers and therapeutic targets for MS, emphasising the need for strategies to rebalance KP metabolism and mitigate neurotoxicity in progressive disease stages.<\/jats:p>","DOI":"10.3390\/ijms26115098","type":"journal-article","created":{"date-parts":[[2025,5,27]],"date-time":"2025-05-27T11:12:57Z","timestamp":1748344377000},"page":"5098","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":15,"title":["Kynurenines and Mitochondrial Disturbances in Multiple Sclerosis"],"prefix":"10.3390","volume":"26","author":[{"ORCID":"https:\/\/orcid.org\/0009-0002-6993-1244","authenticated-orcid":false,"given":"Daniel","family":"Pukoli","sequence":"first","affiliation":[{"name":"Department of Neurology, Esztergomi Vaszary Kolos Hospital, H-2500 Esztergom, Hungary"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"L\u00e1szl\u00f3","family":"V\u00e9csei","sequence":"additional","affiliation":[{"name":"Department of Neurology, Faculty of Medicine, University of Szeged, H-6725 Szeged, Hungary"},{"name":"HUN-REN-SZTE Neuroscience Research Group, Danube Neuroscience Research Laboratory, Hungarian Research Network, University of Szeged (HUN-REN-SZTE), H-6725 Szeged, Hungary"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,5,26]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"43","DOI":"10.1038\/s41572-018-0041-4","article-title":"Multiple sclerosis","volume":"4","author":"Filippi","year":"2018","journal-title":"Nat. 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