The DOI matches its Crossref record; 193 of the 198 references it cites were found in a registry or an index.
Tryptophan Metabolism in Central Nervous System Diseases: Pathophysiology and Potential Therapeutic Strategies
Open accessAbstract
The metabolism of L-tryptophan (TRP) regulates homeostasis, immunity, and neuronal function. Altered TRP metabolism has been implicated in the pathophysiology of various diseases of the central nervous system. TRP is metabolized through two main pathways, the kynurenine pathway and the methoxyindole pathway. First, TRP is metabolized to kynurenine, then kynurenic acid, quinolinic acid, anthranilic acid, 3-hydroxykynurenine, and finally 3-hydroxyanthranilic acid along the kynurenine pathway. Second, TRP is metabolized to serotonin and melatonin along the methoxyindole pathway. In this review, we summarize the biological properties of key metabolites and their pathogenic functions in 12 disorders of the central nervous system: schizophrenia, bipolar disorder, major depressive disorder, spinal cord injury, traumatic brain injury, ischemic stroke, intracerebral hemorrhage, multiple sclerosis, Alzheimer's disease, Parkinson's disease, amyotrophic lateral sclerosis, and Huntington's disease. Furthermore, we summarize preclinical and clinical studies, mainly since 2015, that investigated the metabolic pathway of TRP, focusing on changes in biomarkers of these neurologic disorders, their pathogenic implications, and potential therapeutic strategies targeting this metabolic pathway. This critical, comprehensive, and up-to-date review helps identify promising directions for future preclinical, clinical, and translational research on neuropsychiatric disorders.
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“Moreover, inflammation induces the activation of indoleamine 2,3-dioxygenase (IDO) and diverts TRP metabolism from serotonin to KYN, reducing the availability of CNS-localized serotonin [23].”
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“This aligns with the notion that inflammatory conditions, despite their generation, stimulate TRP degradation and are related to increased levels of KP metabolites in the brain [23], including the neuroprotective KYNA and neurotoxic QUIN [44].”
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Cites
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“The single nucleotide polymorphism of the KMO gene is related to SCZ, further supporting the notion that the decrease in the 3-HK branch in the KP pathway may cause L-KYN to convert to KYNA, which is one of the causes of SCZ [19].”
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“KYNA inhibits endogenous broad-spectrum glutamate receptors, namely, N-methylD-aspartic acid receptors (NMDAR), kainite receptors, and α-amino-3-hydroxy-5-methyl-4-isoxazole-propionic acid receptors (AMPAR) [30].”
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The Association Between Metabolomic and Usual Biochemical Data Helps to Detect Insulin Resistance
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Altered Serotonin Metabolism in Functional Vitamin B12 Deficiency
Russell-Jones, G. (2025) · Journal of Medical - Clinical Research & Reviews · doi:10.33425/2639-944x.1414
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Metadata
- Authors
- Huang, Y., Zhao, M., Chen, X., Zhang, R., Le, A., Hong, M., Zhang, Y., Jia, L., Zang, W., Jiang, C., Wang, J., Fan, X., & Wang, J.
- Affiliations
- First Affiliated Hospital of Zhengzhou University (CN)
- Zhengzhou University (CN)
- Washington University in St. Louis (US)
- Sinai Hospital (US)
- University of Washington (US)
- Fifth Affiliated Hospital of Zhengzhou University (CN)
- Corresponding author
- Wang, Junmin
- Fan, Xiaochong
- Wang, Jian
- ORCID
- Venue
- Aging and disease
- Publisher
- Aging and Disease
- Published
- 2023
- Volume
- 14
- Issue
- 3
- Pages
- 858
- ISSN
- 2152-5250 (ISSN-L)
- PMC
- PMC10187711
- OpenAlex
- W4312580438
- Cited by
- 138
- References
- 198
- Citations by year
- 2026: 45 · 2025: 55 · 2024: 36 · 2023: 2
- FWCI
- 1.76
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- cc-by
- Locations
- Aging and Disease (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Funders
- Zhengzhou University
- Topics
- Life Sciences › Neuroscience › Biological Psychiatry › Tryptophan and brain disorders
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Biochemistry › Amino Acid Enzymes and Metabolism
- Health Sciences › Medicine › Pharmacology (medical) › Treatment of Major Depression
- Keywords
- tryptophan metabolism, kynurenine pathway, central nervous system disorders, schizophrenia, bipolar disorder, major depressive disorder, spinal cord injury, traumatic brain injury, ischemic stroke, intracerebral hemorrhage, multiple sclerosis, Alzheimer's disease, Parkinson's disease, amyotrophic lateral sclerosis, Huntington's disease, kynurenic acid, quinolinic acid, serotonin, melatonin, biomarkers, treatment options
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