{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,8]],"date-time":"2026-10-08T02:33:36Z","timestamp":1791426816948,"version":"4.3.3"},"reference-count":525,"publisher":"MDPI AG","issue":"23","license":[{"start":{"date-parts":[[2024,11,27]],"date-time":"2024-11-27T00:00:00Z","timestamp":1732665600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"National Research, Development, and Innovation Office","award":["NKFIH K138125"],"award-info":[{"award-number":["NKFIH K138125"]}]},{"name":"National Research, Development, and Innovation Office","award":["2022\/5S729"],"award-info":[{"award-number":["2022\/5S729"]}]},{"name":"SZTE SZAOK-KKA","award":["NKFIH K138125"],"award-info":[{"award-number":["NKFIH K138125"]}]},{"name":"SZTE SZAOK-KKA","award":["2022\/5S729"],"award-info":[{"award-number":["2022\/5S729"]}]},{"name":"HUN-REN Hungarian Research Network","award":["NKFIH K138125"],"award-info":[{"award-number":["NKFIH K138125"]}]},{"name":"HUN-REN Hungarian Research Network","award":["2022\/5S729"],"award-info":[{"award-number":["2022\/5S729"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>The tryptophan\u2013kynurenine (KYN) pathway has long been recognized for its essential role in generating metabolites that influence various physiological processes. Traditionally, these metabolites have been categorized into distinct, often opposing groups, such as pro-oxidant versus antioxidant, excitotoxic\/neurotoxic versus neuroprotective. This dichotomous framework has shaped much of the research on conditions like neurodegenerative and neuropsychiatric disorders, as well as cancer, where metabolic imbalances are a key feature. The effects are significantly influenced by various factors, including the concentration of metabolites and the particular cellular milieu in which they are generated. A molecule that acts as neuroprotective at low concentrations may exhibit neurotoxic effects at elevated levels. The oxidative equilibrium of the surrounding environment can alter the function of KYN from an antioxidant to a pro-oxidant. This narrative review offers a comprehensive examination and analysis of the contemporary understanding of KYN metabolites, emphasizing their multifaceted biological functions and their relevance in numerous physiological and pathological processes. This underscores the pressing necessity for a paradigm shift in the comprehension of KYN metabolism. Understanding the context-dependent roles of KYN metabolites is vital for novel therapies in conditions like Alzheimer\u2019s disease, multiple sclerosis, and cancer. Comprehensive pathway modulation, including balancing inflammatory signals and enzyme regulation, offers promising avenues for targeted, effective treatments.<\/jats:p>","DOI":"10.3390\/ijms252312767","type":"journal-article","created":{"date-parts":[[2024,11,27]],"date-time":"2024-11-27T11:26:08Z","timestamp":1732706768000},"page":"12767","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":38,"title":["Redefining Roles: A Paradigm Shift in Tryptophan\u2013Kynurenine Metabolism for Innovative Clinical Applications"],"prefix":"10.3390","volume":"25","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4383-4024","authenticated-orcid":false,"given":"Masaru","family":"Tanaka","sequence":"first","affiliation":[{"name":"HUN-REN-SZTE Neuroscience Research Group, Hungarian Research Network, University of Szeged (HUN-REN-SZTE), Danube Neuroscience Research Laboratory, Tisza Lajos krt. 113, H-6725 Szeged, Hungary"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"\u00c1gnes","family":"Szab\u00f3","sequence":"additional","affiliation":[{"name":"Department of Neurology, Albert Szent-Gy\u00f6rgyi Medical School, University of Szeged, Semmelweis u. 6, H-6725 Szeged, Hungary"},{"name":"Doctoral School of Clinical Medicine, University of Szeged, Kor\u00e1nyi fasor 6, H-6720 Szeged, Hungary"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"L\u00e1szl\u00f3","family":"V\u00e9csei","sequence":"additional","affiliation":[{"name":"HUN-REN-SZTE Neuroscience Research Group, Hungarian Research Network, University of Szeged (HUN-REN-SZTE), Danube Neuroscience Research Laboratory, Tisza Lajos krt. 113, H-6725 Szeged, Hungary"},{"name":"Department of Neurology, Albert Szent-Gy\u00f6rgyi Medical School, University of Szeged, Semmelweis u. 6, H-6725 Szeged, Hungary"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,11,27]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"T\u00f6r\u00f6k, N., Tanaka, M., and V\u00e9csei, L. 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