Tryptophan metabolism: Mechanism-oriented therapy for neurological and psychiatric disorders
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Neurological and psychiatric disorders are a category of chronic diseases that are widespread and pose serious mental and physical health problems for patients. The substrates, products, and enzymes of Tryptophan metabolism all contribute to the development of neurological and psychiatric disorders. This paper deals with three metabolic pathways of tryptophan that produce a series of metabolites called tryptophan Catabolics (TRYCATs). These metabolites are involved in pathological processes such as excitotoxicity, neuroinflammation, oxidative stress, and mitochondrial damage and are closely associated with neurological and psychiatric disorders such as Alzheimer’s disease and depression. Here, we review the elements that affect how tryptophan metabolism is regulated, including inflammation and stress, exercise, vitamins, minerals, diet and gut microbes, glucocorticoids, and aging, as well as the downstream regulatory effects of tryptophan metabolism, including the regulation of glutamate (Glu), immunity, G-protein coupled receptor 35 (Gpr35), nicotinic acetylcholine receptor (nAChR), aryl hydrocarbon receptor (AhR), and dopamine (DA). In order to advance the general understanding of tryptophan metabolism in neurological and psychiatric disorders, this paper also summarizes the current situation and effective drugs of tryptophan metabolism in the treatment of neurological and psychiatric disorders and considers its future research prospects.
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Under inflammatory conditions, tryptophan metabolism shifts towards increased kynurenine levels, leading to an imbalance in downstream metabolites such as quinolinic acid and kynurenic acid.
“Under inflammatory conditions, tryptophan metabolism shifts towards increased kynurenine levels, leading to an imbalance in its downstream metabolites (TRYCATs), such as quinolinic acid (QUIN) and kynurenic acid (KYNA).”
From The Gut–Brain–Microbiota Connection and Its Role in Autism Spectrum Disorders (2025) · cites this paper as [73]
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- Authors
- Li, D., Yu, S., Long, Y., Shi, A., Deng, J., Ma, Y., Wen, J., Li, X., Liu, S., Zhang, Y., Wan, J., Li, N., & Ao, R.
- Affiliations
- Chengdu University of Traditional Chinese Medicine (CN)
- Sichuan Academy of Medical Sciences & Sichuan Provincial People's Hospital (CN)
- Corresponding author
- Li, Nan
- Ao, Rui
- ORCID
- Venue
- Frontiers in Immunology
- Publisher
- Frontiers Media SA
- Published
- 2022-09-08
- Volume
- 13
- Pages
- 985378-985378
- ISSN
- 1664-3224 (ISSN-L)
- PMC
- PMC9496178
- OpenAlex
- W4295865246
- Cited by
- 129
- References
- 136
- Citations by year
- 2026: 27 · 2025: 52 · 2024: 32 · 2023: 18
- FWCI
- 1.93
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- Frontiers in Immunology (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Funders
- Jiangxi University of Traditional Chinese Medicine (zdsys-202107)
- Topics
- Life Sciences › Neuroscience › Biological Psychiatry › Tryptophan and brain disorders
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Biochemistry › Amino Acid Enzymes and Metabolism
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Keywords
- tryptophan metabolism, tryptophan catabolites, neurological disorders, mental illness, Alzheimer's disease, depression, excitotoxicity, neuroinflammation, oxidative stress, mitochondrial damage, gut microbiota, glucocorticoids, aging, glutamate, GPR35, nicotinic acetylcholine receptors, aryl hydrocarbon receptor, dopamine
- MeSH terms
- Mental Disorders, Dopamine, Glucocorticoids, Humans, Receptors, Nicotinic, Tryptophan, Vitamins, Receptors, Aryl Hydrocarbon, Glutamic Acid
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