Neuroinflammation and the Kynurenine Pathway in CNS Disease: Molecular Mechanisms and Therapeutic Implications
Open accessAbstract
Diseases of the central nervous system (CNS) remain a significant health, social and economic problem around the globe. The development of therapeutic strategies for CNS conditions has suffered due to a poor understanding of the underlying pathologies that manifest them. Understanding common etiological origins at the cellular and molecular level is essential to enhance the development of efficacious and targeted treatment options. Over the years, neuroinflammation has been posited as a common link between multiple neurological, neurodegenerative and neuropsychiatric disorders. Processes that precipitate neuroinflammatory conditions including genetics, infections, physical injury and psychosocial factors, like stress and trauma, closely link dysregulation in kynurenine pathway (KP) of tryptophan metabolism as a possible pathophysiological factor that ‘fuel the fire’ in CNS diseases. In this study, we aim to review emerging evidence that provide mechanistic insights between different CNS disorders, neuroinflammation and the KP. We provide a thorough overview of the different branches of the KP pertinent to CNS disease pathology that have therapeutic implications for the development of selected and efficacious treatment strategies.
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The kynurenine pathway is the major route of degradation of tryptophan.
“The kynurenine pathway (KP) is the major route of degradation of TRP [17].”
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Kynurenic Acid Levels are Increased in the CSF of Alzheimer’s Disease Patients
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Endogenous kynurenic acid regulates extracellular GABA levels in the rat prefrontal cortex
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- [295]Valente-Silva P. Ruas J.L. Tryptophan-Kynurenine Metabolites in Exercise and Mental Health BT—Hormones, Metabolism and the Benefits of Exercise Spiegelman B. Springer International Publishing Cham, Germany 2017 83 91 978-3-319-72790-5 31314466
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Microglia in depression: an overview of microglia in the pathogenesis and treatment of depression
Wang, H., He, Y., Sun, Z., Ren, S., Liu, M., Wang, G., & Yang, J. (2022) · Journal of Neuroinflammation · doi:10.1186/s12974-022-02492-0 · Cited by 591 · see citing works
“LPS and other infectious agents, including viruses, upregulate the release of inflammatory cytokines by binding to TLRs, which in turn directly and indirectly induce KP metabolism via pro-inflammatory cytokines [144].”
BackgroundMicrobial-derived metabolites as a risk factor of age-related cognitive decline and dementia
Connell, E., Le Gall, G., Pontifex, M. G., Sami, S., Cryan, J. F., Clarke, G., Müller, M., & Vauzour, D. (2022) · Molecular Neurodegeneration · doi:10.1186/s13024-022-00548-6 · Cited by 208 · see citing works
“Microglia and astrocytes, which contain all of the enzymes necessary for the KP, are the primary effectors of neuroinflammation in AD [214].”
BackgroundHow inflammation affects the brain in depression: a review of functional and structural MRI studies
Han, K.-M., & Ham, B.-J. (2021) · Journal of Clinical Neurology · doi:10.3988/jcn.2021.17.4.503 · Cited by 187 · see citing works
Ortega, M. A., Álvarez-Mon, M. Á., Montero, C. G., Fraile‐Μartinez, O., Monserrat, J., Martinez-Rozas, L., Rodríguez–Jiménez, R., Álvarez‐Mon, M., & Lahera, G. (2023) · Molecular Psychiatry · doi:10.1038/s41380-023-01964-w · Cited by 129 · see citing works
Gao, X., Jiang, M., Huang, N., Guo, X., & Huang, T. (2023) · Environmental Health Perspectives · doi:10.1289/ehp10391 · Cited by 130 · see citing works
“42 Oxidative stress further contributes to the degradation of dopaminergic neurons, which is likely involved in the neuropathology of depression and additionally intimately impairs mitochondrial function, and enhances excitotoxicity and nitric oxide toxicity.”
Tryptophan metabolites in depression: Modulation by gut microbiota
Lukić, I., Ivković, S., Mitić, M., & Adžić, M. (2022) · Frontiers in Behavioral Neuroscience · doi:10.3389/fnbeh.2022.987697 · Cited by 110 · see citing works
“KYNA and QUIN are major kynurenine catabolites with neuroactive properties.”
BackgroundInfluentialTargeting Cytokine-Mediated Inflammation in Brain Disorders: Developing New Treatment Strategies
Mallick, R., Basak, S., Chowdhury, P., Bhowmik, P., Das, R. K., Banerjee, A., Paul, S., Pathak, S., & Duttaroy, A. K. (2025) · Pharmaceuticals · doi:10.3390/ph18010104 · Cited by 94 · see citing works
“For example, kynurenine, a tryptophan metabolite involved in the immune response, has been linked to depression and schizophrenia, demonstrating that the kynurenine pathway is activated in response to inflammation [157,158].”
Sharma, S., Chawla, S., Kumar, P., Ahmad, R., & Verma, P. K. (2024) · Brain Research · doi:10.1016/j.brainres.2024.149123 · Cited by 97 · see citing works
The Influence of Kynurenine Metabolites on Neurodegenerative Pathologies
Pathak, S., Nadar, R. M., Kim, S., Liu, K., Govindarajulu, M., Cook, P., Alexander, C. S. W., Dhanasekaran, M., & Moore, T. (2024) · International Journal of Molecular Sciences · doi:10.3390/ijms25020853 · Cited by 90 · see citing works
Kynurenine Pathway Metabolites as Biomarkers in Alzheimer’s Disease
Liang, Y., Xie, S., He, Y., Xu, M., Qiao, X., Zhu, Y. H., & Wu, W. (2022) · Disease Markers · doi:10.1155/2022/9484217 · Cited by 86 · see citing works
“5-HT (urine, serum), KYN (serum), KYNA (urine), L-TRP (urine, serum), and K/T ratio (urine) were significantly lower in AD patients than in controls.”
BackgroundInfluentialCurrent Understanding of Long-Term Cognitive Impairment After Sepsis
Li, Y., Ji, M., & Yang, J. (2022) · Frontiers in Immunology · doi:10.3389/fimmu.2022.855006 · Cited by 64 · see citing works
Yan, J., Kothur, K., Mohammad, S. S., Chung, J., Patel, S., Jones, H. F., Keating, B. A., Han, V. X., Webster, R., Ardern‐Holmes, S. L., et al. (2023) · EBioMedicine · doi:10.1016/j.ebiom.2023.104589 · Cited by 61 · see citing works
Tanaka, M., Szabó, Á., & Vécsei, L. (2024) · International Journal of Molecular Sciences · doi:10.3390/ijms252312767 · Cited by 62 · see citing works
Kong, Q., Chen, Q., Mao, X., Wang, G., Zhao, J., Zhang, H., & Chen, W. (2022) · Nutrients · doi:10.3390/nu14081615 · Cited by 53 · see citing works
“KP is the main pathway of TRP catabolism, and many studies have indicated that the KP pathway is associated with neurodevelopmental disorders owing to its involvement in neuroprotection and immune regulation [10,32].”
BackgroundJavani, G., Babri, S., Farajdokht, F., Ghaffari‐Nasab, A., & Mohaddes, G. (2022) · Mechanisms of Ageing and Development · doi:10.1016/j.mad.2022.111632 · Cited by 50 · see citing works
Sex Differences in Tryptophan Metabolism: A Systematic Review Focused on Neuropsychiatric Disorders
Pais, M., Martins, J., Castelo-Branco, M. S., & Gonçalves, J. (2023) · International Journal of Molecular Sciences · doi:10.3390/ijms24066010 · Cited by 51 · see citing works
“Since neuroinflammation is a hallmark widely related to neurological and psychiatric diseases [11], many studies explored the possible role of the Tryp oxidation pathway [57,100,101].”
BackgroundCiapała, K., Mika, J., & Rojewska, E. (2021) · International Journal of Molecular Sciences · doi:10.3390/ijms222011055 · Cited by 50 · see citing works
“KMO plays a significant role in the regulation of peripheral inflammation [104] and central nervous system diseases [105].”
BackgroundAğagündüz, D., Çelik, E., Cemali, Ö., Bingöl, F. G., Özenir, Ç., Özoğul, F., & Capasso, R. (2023) · Probiotics and Antimicrobial Proteins · doi:10.1007/s12602-023-10092-4 · Cited by 47 · see citing works
The Kynurenine Pathway in Gut Permeability and Inflammation
Kearns, R. (2024) · Inflammation · doi:10.1007/s10753-024-02135-x · Cited by 37 · see citing works
“…involvement in neuroinflammation and its impact on neurotransmitter systems, including glutamatergic, GABAergic, dopaminergic, and noradrenergic neurotransmissions, underscores its importance in brain function and the pathogenesis of disorders such as depression and neurodegeneration [48, 81, 114].”
Strumila, R., Nobile, B., Korsakova, L., Lengvenytė, A., Olié, É., López‐Castromán, J., Guillaume, S., & Courtet, P. (2021) · Pharmaceuticals · doi:10.3390/ph14121213 · Cited by 37 · see citing works
PTSD, Immune System, and Inflammation
Pivac, N., Vuić, B., Šagud, M., Erjavec, G. N., Perković, M. N., Konjevod, M., Tudor, L., Štrac, D. Š., Uzun, S., Kozumplik, O., et al. (2023) · Advances in experimental medicine and biology · doi:10.1007/978-981-19-7376-5_11 · Cited by 38 · see citing works
Iqbal, M. K., Khan, B., Hifsa, H., YuXuan, G., Mujahid, M., Kiyani, M. M., Khan, H. R., & Bashir, S. (2024) · ACS Omega · doi:10.1021/acsomega.4c06546 · Cited by 34 · see citing works
Tiwari, S., & Paramanik, V. (2025) · Molecular Neurobiology · doi:10.1007/s12035-025-04708-9 · Cited by 37 · see citing works
“The harmful action of Trp/kynurenine metabolites may be responsible for the oxidative damage, neuroinflammation, and mitochondrial dysfunction [63].”
Dietary Kynurenine Pathway Metabolites—Source, Fate, and Chromatographic Determinations
Sadok, I., & Jędruchniewicz, K. (2023) · International Journal of Molecular Sciences · doi:10.3390/ijms242216304 · Cited by 32 · see citing works
Quinoline Quest: Kynurenic Acid Strategies for Next-Generation Therapeutics via Rational Drug Design
Tanaka, M., Szatmári, I., & Vécsei, L. (2025) · Pharmaceuticals · doi:10.3390/ph18050607 · Cited by 35 · see citing works
Kynurenines as a Novel Target for the Treatment of Inflammatory Disorders
Mor, A., Tankiewicz‐Kwedlo, A., Ciwun, M., Lewkowicz, J., & Pawlak, D. (2024) · Cells · doi:10.3390/cells13151259 · Cited by 29 · see citing works
Cellular Localization of Kynurenine 3-Monooxygenase in the Brain: Challenging the Dogma
Sathyasaikumar, K. V., de la Cruz, V. P., Pineda, B., Cervantes, G. I. V., Ortega, D. R., Donley, D., Severson, P., West, B., Giorgini, F., Fox, J. H., et al. (2022) · Antioxidants · doi:10.3390/antiox11020315 · Cited by 25 · see citing works
“Considering the complexities of cerebral KP function [1] as well as the critical role of peripherally derived kynurenine [87], special attention ought to be paid to additional cell types such as oligodendrocytes [88] and perivascular cells [89], and to the evaluation of brain region-specific heterogeneities.”
BackgroundInfluentialHow inflammation influences psychiatric disease
Ferat-Osorio, E. A., Maldonado-García, J. L., & Pavón, L. (2024) · World Journal of Psychiatry · doi:10.5498/wjp.v14.i3.342 · Cited by 29 · see citing works
Martos, D., Lőrinczi, B., Szatmári, I., Vécsei, L., & Tanaka, M. (2024) · International Journal of Molecular Sciences · doi:10.3390/ijms25063394 · Cited by 25 · see citing works
VanderZwaag, J., Halvorson, T., Dolhan, K., Šimončičová, E., Ben‐Azu, B., & Tremblay, M. (2022) · Neurochemical Research · doi:10.1007/s11064-022-03772-0 · Cited by 26 · see citing works
The Kynurenine Pathway, Aryl Hydrocarbon Receptor, and Alzheimer’s Disease
Cortés-Malagón, E. M., Ornelas, A. L., Olvera‐Gómez, I., & Bonilla‐Delgado, J. (2024) · Brain Sciences · doi:10.3390/brainsci14090950 · Cited by 25 · see citing works
“The neuroinflammation and kynurenine pathway (KP) are closely connected and play a fundamental role in various neurological conditions [37].”
BackgroundXu, L., Zhao, Z., Zhang, Y., & Ma, C.-L. (2025) · Journal of Neuroinflammation · doi:10.1186/s12974-025-03553-w · Cited by 27 · see citing works
Kynurenine pathway and its role in neurologic, psychiatric, and inflammatory bowel diseases
Sheibani, M., Shayan, M., Khalilzadeh, M., Soltani, Z. E., Jafari‐Sabet, M., Ghasemi, M., & Dehpour, A. R. (2023) · Molecular Biology Reports · doi:10.1007/s11033-023-08859-7 · Cited by 24 · see citing works
Luo, Y., Jiang, N., Zhang, Y., Zhao, Y., Chen, F., Li, X., Qiang, M., Zeng, G., He, Q., Liu, X., et al. (2025) · Frontiers in Neuroscience · doi:10.3389/fnins.2025.1556744 · Cited by 23 · see citing works
Shokr, M. M., Eladawy, R. M., Azar, Y. O., & Raish, S. M. A. (2025) · Foods · doi:10.3390/foods14172926 · Cited by 23 · see citing works
“Excessive microglia produce neurotoxic chemicals that cause neuroin-flammation and depressive-like behavior by over-activating the shunt tryptophan from serotonin production into the kynurenine pathway (KP) [34,38].”
Kynurenine Pathway Metabolites as Potential Biomarkers in Chronic Pain
Auyeung, A., Wang, H. C., Aravagiri, K., & Knezevic, N. (2023) · Pharmaceuticals · doi:10.3390/ph16050681 · Cited by 20 · see citing works
“Production of QA is greatly increased during an immune response, the mechanism of which is suspected to be via the activation of IDO-1, IDO-2, and TDO by inflammatory cytokines (primarily IFN gamma) [42].”
BackgroundTanaka, M., & Vécsei, L. (2024) · Journal of Neural Transmission · doi:10.1007/s00702-024-02812-z · Cited by 23 · see citing works
Yan, J., Han, V. X., Heng, B., Guillemin, G. J., Bandodkar, S., & Dale, R. C. (2022) · EBioMedicine · doi:10.1016/j.ebiom.2022.103917 · Cited by 22 · see citing works
Xanthurenic acid: A role in brain intercellular signaling
Maître, M., Taleb, O., Jeltsch‐David, H., Klein, C., & Mensah‐Nyagan, A. G. (2024) · Journal of Neurochemistry · doi:10.1111/jnc.16099 · Cited by 22 · see citing works
Quinolinic acid potentially links kidney injury to brain toxicity
Saliba, A., Debnath, S., Tamayo, I. M., Lee, H. J., Ragi, N., Das, F., Montellano, R., Tůmová, J., Maddox, M., Trevino, E., et al. (2025) · JCI Insight · doi:10.1172/jci.insight.180229 · Cited by 20 · see citing works
“Inflammation leading to Trp oxidative degradation is widely supported by previous studies (30–32).”
Self-citationSong, J.-J., Li, H., Wang, N., Zhou, X., Liu, Y., Zhang, Z., Qian, F., Chen, Y., Liu, D., Liang, J., et al. (2022) · Frontiers in Pharmacology · doi:10.3389/fphar.2022.1044375 · Cited by 20 · see citing works
“Neuroinflammation is now recognized as one of the most shared pathologies in multiple CNS disorders (Mithaiwala et al., 2021).”
BackgroundNicotinamide Adenine Dinucleotide Deficiency and Its Impact on Mammalian Development
Dunwoodie, S. L., Bozon, K., Szot, J. O., & Cuny, H. (2023) · Antioxidants and Redox Signaling · doi:10.1089/ars.2023.0349 · Cited by 20 · see citing works
Li, Q., Ma, Q., Zhou, Y., Jiang, X., Parales, R. E., Zhao, S., Zhuang, Y., & Ruan, Z. (2024) · Journal of Hazardous Materials · doi:10.1016/j.jhazmat.2024.134951 · Cited by 20 · see citing works
Yang, S., Han, J., Ye, Z., Zhou, H., Yan, Y., Han, D., Chen, S., Wang, L., Feng, Q., Zhao, X., et al. (2024) · European Child & Adolescent Psychiatry · doi:10.1007/s00787-024-02579-4 · Cited by 19 · see citing works
Early-life stress and the gut microbiome: A comprehensive population-based investigation
Mulder, R. H., Kraaij, R., Schuurmans, I. K., Francés‐Cuesta, C., Sanz, Y., Medina‐Gómez, C., Duijts, L., Rivadeneira, F., Tiemeier, H. W., Jaddoe, V. W. V., et al. (2024) · Brain Behavior and Immunity · doi:10.1016/j.bbi.2024.02.024 · Cited by 18 · see citing works
“…implicated in mood and typically targeted by antidepressants – which, unlike serotonin, can cross the blood – brain barrier to the central nervous system and plays a role in modulation of both peripheral and central neuroinflammatory responses (Mithaiwala et al., 2021; Seo and Kwon, 2023).”
BackgroundSathyasaikumar, K. V., Notarangelo, F. M., Kelly, D. L., Rowland, L. M., Hare, S., Chen, S., Chen, M., Buchanan, R. W., & Schwarcz, R. M. (2022) · Pharmaceuticals · doi:10.3390/ph15081003 · Cited by 18 · see citing works
Sathyasaikumar, K. V., Ayala, T. B., Zheng, Y., Schwieler, L., Erhardt, S., Tufvesson‐Alm, M., Pöeggeler, B., & Schwarcz, R. M. (2024) · International Journal of Tryptophan Research · doi:10.1177/11786469241262876 · Cited by 18 · see citing works
Chen, X., Yin, X., Wang, C.-C., Du, P., Wang, X., Lu, Y., Sun, Y., Sun, Y.-H., & Hu, Y.-M. (2022) · Neural Regeneration Research · doi:10.4103/1673-5374.343885 · Cited by 18 · see citing works
Cavaleri, D., Crocamo, C., Morello, P., Bartoli, F., & Carrà, G. (2024) · Journal of Clinical Medicine · doi:10.3390/jcm13020583 · Cited by 15 · see citing works
“The association of lower serum KYNA with higher serum KYN in people with ADHD shown by our meta-analysis may thus corroborate the hypothesis of a decreased activity of enzyme KAT, a key intermediate in the KP which—unlike IDO and KMO—is not induced or upregulated by inflammation [67].”
ResultQin, W., Shi, Y., Chen, W., Jia, X., & Asakawa, T. (2022) · BioScience Trends · doi:10.5582/bst.2022.01352 · Cited by 16 · see citing works
“Therefore, we believe that the KP plays a key role in "delivering aging signal" from the periphery to the CNS, thereby contributing to the regulation of inflammatory processes in the CNS (46,47).”
BackgroundRen, H., Lin, F., Wu, L., Tan, L., Lu, L., Xie, X., Zhang, Y., Bao, Y., Ma, Y., Huang, X., et al. (2022) · Behavioural Brain Research · doi:10.1016/j.bbr.2022.114237 · Cited by 15 · see citing works
Neuroimmunometabolism: how metabolism orchestrates immune response in healthy and diseased brain
Rana, A. K., Bhatt, B., Gusain, C., Biswal, S., Das, D., & Kumar, M. (2025) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.00331.2024 · Cited by 15 · see citing works
Mohammadgholi-Beiki, A., Sheibani, M., Jafari‐Sabet, M., Motevalian, M., & Rahimi‐Moghaddam, P. (2024) · International Immunopharmacology · doi:10.1016/j.intimp.2024.112158 · Cited by 15 · see citing works
The Power Struggle: Kynurenine Pathway Enzyme Knockouts and Brain Mitochondrial Respiration
Juhász, L., Spisák, K., Szolnoki, B. Z., Nászai, A., Szabó, Á., Rutai, A., Tallósy, S. P., Szabó, A., Toldi, J., Tanaka, M., et al. (2025) · Journal of Neurochemistry · doi:10.1111/jnc.70075 · Cited by 15 · see citing works
“The tryptophan (Trp)- kynurenine (KYN) metabolic pathway is currently being extensively studied as a potential new target for intervention, due to its crucial involvement in various neurological conditions (Fujigaki et al. 2017; Mithaiwala et al. 2021).”
From orphan to oncogene: The role of GPR35 in cancer and immune modulation
Takkar, S., Sharma, G., Kaushal, J., Abdullah, K. M., Batra, S. K., & Siddiqui, J. A. (2024) · Cytokine & Growth Factor Reviews · doi:10.1016/j.cytogfr.2024.03.004 · Cited by 14 · see citing works
Tian, Y., Meng, J., Zhang, D., Zhai, B., Cheng, J., Zou, J., Shi, Y., & Guo, D. (2025) · Phytomedicine · doi:10.1016/j.phymed.2025.157028 · Cited by 14 · see citing works
Marković, M., Petronijević, N., Stašević, M., Karličić, I. S., Velimirović, M., Stojković, T., Ristić, S., Stojković, M., Milic, N. M., & Nikolić, T. (2023) · Cells · doi:10.3390/cells12242814 · Cited by 11 · see citing works
Wang, H., Zhai, Y., Lei, Z., Chen, S., Sun, M., Yin, P., Duan, Z., & Wang, X. (2023) · Frontiers in Immunology · doi:10.3389/fimmu.2023.1171351 · Cited by 14 · see citing works
Sadeghi, M. A., Hemmati, S., Yousefi‐Manesh, H., Foroutani, L., Nassireslami, E., Zoshk, M. Y., Hosseini, Y., Abbasian, K., Dehpour, A. R., & Chamanara, M. (2023) · Naunyn-Schmiedeberg s Archives of Pharmacology · doi:10.1007/s00210-023-02578-3 · Cited by 14 · see citing works
“Continued activity of the kynurenine pathway through increased IDO expression and the prominence of its oxidative branch in a neuroinflammatory environment (stimulation of KMO by IL-1β) leads to excess production of 3-hydroxykynurenine and quinolinic acid (Mithaiwala et al. 2021).”
InfluentialBose, M. M., Govindula, A., Nampoothiri, M., Arora, D. S., & Mudgal, J. (2025) · Pharmacological Reports · doi:10.1007/s43440-025-00806-6 · Cited by 13 · see citing works
Inam, M. E., Fernandes, B. S., Salagre, E., Grande, I., Vieta, E., Quevedo, J., & Zhao, Z. (2023) · Brazilian Journal of Psychiatry · doi:10.47626/1516-4446-2022-2973 · Cited by 15 · see citing works
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“Metabolic disorders of the kynurenine pathway are closely related to nervous system diseases (Zhang et al., 2020; Chen et al., 2021; Mithaiwala et al., 2021).”
BackgroundExploring novel non-opioid pathways and therapeutics for pain modulation
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“54,55”
Altered Tryptophan-Kynurenine Pathway in Delirium: A Review of the Current Literature
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“The KP is upregulated in response to immune system activation, and produces various neuroactive metabolites that are able to influence the function on brain innate immune cells [32].”
BackgroundKaur, M., Porel, P., Patel, R., & Aran, K. R. (2025) · Neurotoxicity Research · doi:10.1007/s12640-025-00738-2 · Cited by 12 · see citing works
“Kynurenine is converted to kynurenic acid by the enzymes KAT I and KAT III, which easily exit mitochondria (Mithaiwala et al. 2021).”
Ferroptosis: a new target for depression prevention and treatment
Liang, W., Guo, H., Li, L., Tan, W., Liu, J., Hu, X., Wang, Y., & Zhou, S. (2025) · Journal of Neural Transmission · doi:10.1007/s00702-025-02912-4 · Cited by 12 · see citing works
“Neuroendogenous toxicity induced by canine uric acid and quinolinic acid (Mithaiwala et al. 2021) may be associated with iron deposition; excess iron may affect the synthesis and release of neurotransmitters like dopamine (DA), impairing normal brain function.”
Boberg, E., Kadri, N., Hagey, D. W., Schwieler, L., Andaloussi, S. E., Erhardt, S., Iacobaeus, E., & Blanc, K. L. (2023) · Leukemia · doi:10.1038/s41375-023-01840-0 · Cited by 12 · see citing works
“Leukemia (2023) 37:888 – 900 tryptophan 2,3-dioxygenase (TDO, Fig.”
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Citalopram Neuroendocrine Challenge Shows Altered Tryptophan and Kynurenine Metabolism in Migraine
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“KYN contributes to chemotactic activation of peripheral monocytes and also has a potential neuroimmunoregulatory role [28,30], while accumulating evidence suggests that alteration of the serotonin level in the body by serotonin reuptake inhibitors (SSRIs) modulates immune cell function and cytokine production [31].”
BackgroundMethodInnovation in nanomedicine: nanocarriers for central nervous system disorders management
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“Neurodegenerative diseases (NDs) are conditions that occur either randomly or due to genetic factors, and are characterized by the progressive and slow decline of specific types of nerve cells [17,18] .”
Neurological Infection, Kynurenine Pathway, and Parasitic Infection by Neospora caninum
Del'arco, A. E., Argolo, D., Guillemin, G., Costa, M. D. F. D., Costa, S., & Pinheiro, A. M. (2022) · Frontiers in Immunology · doi:10.3389/fimmu.2021.714248 · Cited by 9 · see citing works
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Does the kynurenine pathway play a pathogenic role in autism spectrum disorder?
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“Alternatively, kynurenine 3-hydroxylase (KMO) can convert KYN to 3-hydroxykynurenine (3-HK), a precursor of quinolinic acid (QUIN) (Mithaiwala et al., 2021).”
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“KYNU is involved in tryptophan metabolism via the kynurenine pathway, and neuroinflammation — a hallmark of AD — can disrupt this pathway, potentially lowering KYNU levels [25 – 27].”
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New Perspective on Anorexia Nervosa: Tryptophan-Kynurenine Pathway Hypothesis
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“The hypothesis linking neuroinflammation with increased metabolism of TRP along the KP and its shift towards neurotoxic kynurenines is well substantiated [17,36,37].”
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“While lower concentrations of 3-HK contribute to the neurotoxic profile described earlier, higher concentrations can support cellular antioxidant defenses [113].”
Anti-Inflammatory Therapy as a Promising Target in Neuropsychiatric Disorders
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“Although the association between MDD and sirtuin [27] and kynurenine pathway (KP) [28] has been widely reviewed previously, the association between MDD and NAD and its related pathways are still lacking.”
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Activation of the kynurenine pathway identified in individuals with covert hepatic encephalopathy
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de Oliveira, F. R., Appenzeller, S., Pasoto, S. G., Fernandes, M. L. M. S., Lopes, M. L. L., Fialho, S. C. D. M. S., Pinheiro, A. C., dos Santos, L. C., Valim, V., Serrano, É. V., et al. (2025) · Revista Brasileira de Reumatologia · doi:10.1186/s42358-025-00438-7 · Cited by 8 · see citing works
“Given the broad spectrum of presentations, different pathogenic mechanisms respond to neurological injuries and symptoms [27, 28, 37–39].”
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“For instance, inflammatory responses can decrease the levels of the amino acid tryptophan via increased metabolism along the kynurenine pathway, which directly and indirectly influences multiple neurotransmitter systems [6,7].”
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“This study highlighted the involvement of quinolinic acid in the inflammatory cascades [26, 33].”
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“A potential role of the communication between kynurenine and neuroinflammatory pathway (Mithaiwala et al, 2021) in the survival mechanism can be addressed in future investigation.”
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Kynurenines in the Pathogenesis of Peripheral Neuropathy During Leprosy and COVID-19
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“An agonist action of QUIN toward NMDA receptors was reported (Stone and Perkins, 1981; Mithaiwala et al., 2021).”
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Inflammation and treatment strategies for suicidal behavior
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“However, enzyme KAT is not upregulated or induced in response to inflammation, which affects the QUIN:KYNA balance towards the neurotoxic branch (Campbell et al. 2014; Mithaiwala et al. 2021).”
- Authors
- Mithaiwala, M. N., Santana-Coelho, D., Porter, G. A., & O’Connor, J. C.
- Affiliations
- The University of Texas at San Antonio Health Science Center (US)
- Integrated Biomedical Sciences Program, Graduate School of Biomedical Sciences, UT Health San Antonio, San Antonio, TX 78229, USA
- Corresponding author
- O’Connor, Jason C.
- Venue
- Cells
- Publisher
- MDPI AG
- Published
- 2021-06-19
- Volume
- 10
- Issue
- 6
- Pages
- 1548
- ISSN
- 2073-4409 (ISSN-L)
- PMC
- PMC8235708
- OpenAlex
- W3174682784
- Cited by
- 190
- References
- 303
- Citations by year
- 2026: 35 · 2025: 44 · 2024: 46 · 2023: 32 · 2022: 28 · 2021: 3 · 2013: 1
- FWCI
- 2.57
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- Cells (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Funders
- U.S. Department of Veterans Affairs (I01BX003195)
- National Institutes of Health (TR002645, TR002647)
- Topics
- Life Sciences › Neuroscience › Biological Psychiatry › Tryptophan and brain disorders
- Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
- Health Sciences › Medicine › Psychiatry and Mental health › Migraine and Headache Studies
- Keywords
- neuroinflammation, kynurenine pathway, tryptophan metabolism, central nervous system disorders, neurodegenerative diseases, neuropsychiatric disorders, therapeutic target
- MeSH terms
- Animals, Mental Disorders, Humans, Inflammation, Kynurenine, Neurodegenerative Diseases
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