{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,24]],"date-time":"2026-03-24T09:01:51Z","timestamp":1774342911613,"version":"3.50.1"},"reference-count":45,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2026,3,21]],"date-time":"2026-03-21T00:00:00Z","timestamp":1774051200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pharmaceuticals"],"abstract":"<jats:p>Background\/Objectives: Multiple Sclerosis (MS) is a chronic immune-mediated disorder characterized by neuroinflammation and neurodegeneration. Increasing evidence implies the kynurenine pathway (KP) in the MS pathophysiology; however, data from Mexican populations are lacking. This exploratory study aimed to characterize central and circulating KP metabolites in Mexican patients with MS and to investigate potential genetic variants in KP-related genes. Methods: Serum concentrations of kynurenic acid (KYNA) and 3-hydroxykynurenine (3-HK), as well as cerebrospinal fluid (CSF) levels of KYNA, quinolinic acid (QUIN), interleukin-4 (IL-4), and interleukin-6 (IL-6), were determined in treatment-na\u00efve relapsing-remitting MS (RRMS), primary progressive MS (PPMS), and treated PMS patients. Serum levels were compared with those of healthy controls, and CSF findings contrasted with those of non-MS neurological patients and individuals with neurocysticercosis (NCC). Public whole-exome datasets were analyzed for variants in KP-related genes, and target exome sequencing was performed in three Mexican patients with MS. Results: Serum concentrations of KYNA and 3-HK were decreased in MS patients compared with healthy controls. CSF KYNA and QUIN levels did not differ significantly among MS subtypes or the non-MS neurological group, but they were lower than those observed in NCC. IL-4 and IL-6 were detectable in MS CSF samples, supporting the presence of intrathecal inflammation. Genetic and bioinformatic analyses identified variants in genes encoding KP enzymes in both public MS datasets and in Mexican patients with MS. Conclusions: These findings indicate an altered KP metabolism in Mexican MS patients, particularly during the relapse phase, and suggest a possible contribution of genetic variability. Further large-scale studies are needed to confirm these observations and to determine the functional implications of KP-related genetic variants in MS.<\/jats:p>","DOI":"10.3390\/ph19030513","type":"journal-article","created":{"date-parts":[[2026,3,23]],"date-time":"2026-03-23T13:07:06Z","timestamp":1774271226000},"page":"513","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Central and Peripheral Characterization of Key Kynurenine Pathway Metabolites in Mexican Patients with Multiple Sclerosis: An Exploratory Study"],"prefix":"10.3390","volume":"19","author":[{"ORCID":"https:\/\/orcid.org\/0009-0005-9107-6549","authenticated-orcid":false,"given":"Pablo Arturo","family":"Acosta Mendez","sequence":"first","affiliation":[{"name":"Neurobiochemistry and Behavior Laboratory, National Institute of Neurology and Neurosurgery \u201cManuel Velasco Su\u00e1rez\u201d, Mexico City 14269, Mexico"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Graciela","family":"Ordo\u00f1ez","sequence":"additional","affiliation":[{"name":"Neuroimmunology Department, National Institute of Neurology and Neurosurgery \u201cManuel Velasco Su\u00e1rez\u201d, Mexico City 14269, Mexico"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0095-2357","authenticated-orcid":false,"given":"Karla F.","family":"Meza-Sosa","sequence":"additional","affiliation":[{"name":"Neurobiochemistry and Behavior Laboratory, National Institute of Neurology and Neurosurgery \u201cManuel Velasco Su\u00e1rez\u201d, Mexico City 14269, Mexico"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8235-4723","authenticated-orcid":false,"given":"Tonali","family":"Blanco Ayala","sequence":"additional","affiliation":[{"name":"Neurobiochemistry and Behavior Laboratory, National Institute of Neurology and Neurosurgery \u201cManuel Velasco Su\u00e1rez\u201d, Mexico City 14269, Mexico"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8610-7404","authenticated-orcid":false,"given":"Daniela","family":"Ramirez Ortega","sequence":"additional","affiliation":[{"name":"Neurobiochemistry and Behavior Laboratory, National Institute of Neurology and Neurosurgery \u201cManuel Velasco Su\u00e1rez\u201d, Mexico City 14269, Mexico"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4268-0142","authenticated-orcid":false,"given":"Gonzalo","family":"P\u00e9rez de la Cruz","sequence":"additional","affiliation":[{"name":"Department of Mathematics, Faculty of Sciences, Universidad Nacional Aut\u00f3noma de M\u00e9xico (UNAM), Mexico City 04510, Mexico"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8262-3399","authenticated-orcid":false,"given":"Dinora F.","family":"Gonz\u00e1lez Esquivel","sequence":"additional","affiliation":[{"name":"Neurobiochemistry and Behavior Laboratory, National Institute of Neurology and Neurosurgery \u201cManuel Velasco Su\u00e1rez\u201d, Mexico City 14269, Mexico"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9324-229X","authenticated-orcid":false,"given":"Teresita","family":"Corona","sequence":"additional","affiliation":[{"name":"Clinical Laboratory of Neurodegenerative Diseases, National Institute of Neurology and Neurosurgery \u201cManuel Velasco Su\u00e1rez\u201d, Mexico City 14269, Mexico"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jos\u00e9","family":"Flores Rivera","sequence":"additional","affiliation":[{"name":"Multiple Sclerosis and Demyelinating Disorders Clinic, National Institute of Neurology and Neurosurgery \u201cManuel Velasco Su\u00e1rez\u201d, Mexico City 14269, Mexico"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ver\u00f3nica","family":"Rivas","sequence":"additional","affiliation":[{"name":"Multiple Sclerosis and Demyelinating Disorders Clinic, National Institute of Neurology and Neurosurgery \u201cManuel Velasco Su\u00e1rez\u201d, Mexico City 14269, Mexico"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Paul","family":"Carrillo Mora","sequence":"additional","affiliation":[{"name":"Clinical Neurosciences Division, National Institute of Rehabilitation \u201cLuis Guillermo Ibarra Ibarra\u201d, Mexico City 14389, Mexico"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1042-8505","authenticated-orcid":false,"given":"Carmen","family":"Al\u00e1ez-Verson","sequence":"additional","affiliation":[{"name":"Laboratory of Genomic Diagnostics, National Institute of Genomic Medicine, Mexico City 14610, Mexico"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Korrapati V.","family":"Sathyasaikumar","sequence":"additional","affiliation":[{"name":"Maryland Psychiatric Research Center, Department of Psychiatry, University of Maryland School of Medicine, Baltimore, MD 21228, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2095-9182","authenticated-orcid":false,"given":"Sa\u00fal","family":"Gomez-Manzo","sequence":"additional","affiliation":[{"name":"Laboratorio de Bioqu\u00edmica Gen\u00e9tica, Instituto Nacional de Pediatr\u00eda, Secretar\u00eda de Salud, Mexico City 04530, Mexico"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Aleli","family":"Salazar","sequence":"additional","affiliation":[{"name":"Neuroimmunology Department, National Institute of Neurology and Neurosurgery \u201cManuel Velasco Su\u00e1rez\u201d, Mexico City 14269, Mexico"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1455-312X","authenticated-orcid":false,"given":"Benjamin","family":"Pineda","sequence":"additional","affiliation":[{"name":"Neuroimmunology Department, National Institute of Neurology and Neurosurgery \u201cManuel Velasco Su\u00e1rez\u201d, Mexico City 14269, Mexico"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1451-8754","authenticated-orcid":false,"given":"Ver\u00f3nica","family":"P\u00e9rez de la Cruz","sequence":"additional","affiliation":[{"name":"Neurobiochemistry and Behavior Laboratory, National Institute of Neurology and Neurosurgery \u201cManuel Velasco Su\u00e1rez\u201d, Mexico City 14269, 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