{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,17]],"date-time":"2026-07-17T04:04:29Z","timestamp":1784261069539,"version":"3.55.0"},"reference-count":251,"publisher":"MDPI AG","issue":"14","license":[{"start":{"date-parts":[[2026,7,16]],"date-time":"2026-07-16T00:00:00Z","timestamp":1784160000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>The kynurenine pathway (KP) constitutes the primary route of tryptophan catabolism, generating a spectrum of neuroactive metabolites that profoundly influence central nervous system function. Dysregulation of the KP is increasingly recognized as a critical pathogenic mechanism underlying diverse neuropathological conditions. This review critically evaluates the most widely cited mammalian cellular models currently utilized to delineate the causal role of KP alterations in neurological disease. Specifically, this article examines primary cell cultures, immortalized and tumor-derived cell lines, stem cell-derived systems, and ex vivo organotypic brain slices and tissues, highlighting their distinct methodological advantages, translational limitations, and specific enzymatic profiles. Across the described cellular systems, a recurring mechanistic theme emerges: quinolinic acid-driven mitochondrial dysfunction, oxidative stress, and NAD+ depletion converge in neurodegenerative conditions such as Alzheimer\u2019s disease, Huntington\u2019s disease, and amyotrophic lateral sclerosis. Conversely, kynurenic acid exhibits disorder-dependent\u2014and at times opposing\u2014roles, attenuating dopaminergic neurotoxicity in Parkinson\u2019s disease models while contributing to synaptic pruning deficits in schizophrenia models. Furthermore, cellular models demonstrate that IDO1\/TDO induction and downstream metabolite shifts are frequently cell type- and species-dependent, complicating direct extrapolation to human pathology. Because no single experimental system achieves complete physiological fidelity, elucidating the complex dynamics of the KP and identifying novel therapeutic targets requires the integration of data across complementary platforms.<\/jats:p>","DOI":"10.3390\/ijms27146337","type":"journal-article","created":{"date-parts":[[2026,7,17]],"date-time":"2026-07-17T03:12:38Z","timestamp":1784257958000},"page":"6337","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["The Kynurenine Pathway: Unraveling Its Role in Neurological Disorders via Mammalian Cellular Models"],"prefix":"10.3390","volume":"27","author":[{"ORCID":"https:\/\/orcid.org\/0009-0002-4275-847X","authenticated-orcid":false,"given":"Elizaveta S.","family":"Podshivalova","sequence":"first","affiliation":[{"name":"Research Centre for Medical Genetics, 115522 Moscow, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sergey I.","family":"Kutsev","sequence":"additional","affiliation":[{"name":"Research Centre for Medical Genetics, 115522 Moscow, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aleksandr V.","family":"Shestopalov","sequence":"additional","affiliation":[{"name":"Research Centre for Medical Genetics, 115522 Moscow, Russia"},{"name":"Department of Biochemistry and Molecular Biology, Pirogov Russian National Research Medical University, 117513 Moscow, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,7,16]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"131","DOI":"10.1038\/s41380-019-0414-4","article-title":"The Kynurenine Pathway: A Finger in Every Pie","volume":"25","author":"Savitz","year":"2020","journal-title":"Mol. 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