Modulation of T cells by tryptophan metabolites in the kynurenine pathway

Trends in Pharmacological Sciences, Год журнала: 2023, Номер 44(7), С. 442 - 456

Опубликована: Май 27, 2023

Lymphocytes maturing in the thymus (T cells) are key factors adaptive immunity and regulation of inflammation. The kynurenine pathway tryptophan metabolism includes several enzymes compounds that can modulate T cell function, but manipulating these pharmacologically has not achieved expected therapeutic activity for treatment autoimmune disorders cancer. With increasing knowledge other pathways interacting with kynurenines, expansion screening methods, application virtual techniques to understanding enzyme structures mechanisms, details interactions between kynurenines being revealed. This review surveys some alternative approaches influence function indirectly via summarizes most recent work on development acting directly pathway.

Язык: Английский

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The Tryptophan and Kynurenine Pathway Involved in the Development of Immune-Related Diseases

International Journal of Molecular Sciences, Год журнала: 2023, Номер 24(6), С. 5742 - 5742

Опубликована: Март 17, 2023

The tryptophan and kynurenine pathway is well-known to play an important role in nervous, endocrine, immune systems, as well the development of inflammatory diseases. It has been documented that some metabolites are considered have anti-oxidative, anti-inflammatory, and/or neuroprotective properties. Importantly, many these may possess immune-regulatory properties could alleviate inflammation response. abnormal activation might be involved pathophysiological process various immune-related diseases, such bowel disease, cardiovascular osteoporosis, polycystic ovary syndrome. Interestingly, brain memory system intricate immunity via modulation glial function. In further deliberation this concept with engram, roles gut microbiota lead remarkable treatments for prevention therapeutics intractable

Язык: Английский

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Interactions of IDO and the Kynurenine Pathway with Cell Transduction Systems and Metabolism at the Inflammation–Cancer Interface

Cancers, Год журнала: 2023, Номер 15(11), С. 2895 - 2895

Опубликована: Май 24, 2023

The mechanisms underlying a relationship between inflammation and cancer are unclear, but much emphasis has been placed on the role of tryptophan metabolism to kynurenine downstream metabolites, as these make substantial contribution regulation immune tolerance susceptibility cancer. proposed link is supported by induction indoleamine-2,3-dioxygenase (IDO) or tryptophan-2,3-dioxygenase (TDO), in response injury, infection stress. This review will summarize pathway then focus bi-directional interactions with other transduction pathways cancer-related factors. can interact modify activity many systems, potentially generating an extended web effects than direct its metabolites. Conversely, pharmacological targeting those systems could greatly enhance efficacy changes pathway. Indeed, manipulating interacting affect inflammatory status tumor development indirectly via pathway, while modulation influence anti-cancer protection. While current efforts progressing account for failure selective IDO1 inhibitors inhibit growth devise means circumventing issue, it clear that there wider factors involving kynurenines merit detailed consideration alternative drug targets.

Язык: Английский

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Changes in kynurenine metabolites in the gray and white matter of the dorsolateral prefrontal cortex of individuals affected by schizophrenia

Schizophrenia, Год журнала: 2024, Номер 10(1)

Опубликована: Фев. 27, 2024

Abstract Alterations in the kynurenine pathway of tryptophan metabolism have been implicated pathophysiology schizophrenia. Here, we performed an in-depth analysis all metabolites pathway, i.e., (TRY), kynurenic acid (KYNA), L-kynurenine (KYN), 3-hydroxykynurenine (3-HK), anthranylic (ANA), 3-hydroxyanthranylic (3-HANA), xanthurenic (XA) and quinolinic (QUINA), postmortem samples dorsolateral prefrontal cortex (DLPFC, Brodmann area 46, 9) individuals affected by schizophrenia non-schizophrenic controls. The was carried out gray white matter. Levels KYN, 3-HK, ANA, 3-HANA were significantly increased both matter DLPFC schizophrenia, whereas levels TRY, KYNA, QUINA exclusively remained unchanged These increases did not correlate with age, sex, duration disease, type antipsychotic medication. findings suggest that two major branches transamination KYN into hydroxylation 3-HK are activated perhaps as a result neuroinflammation, support evidence abnormalities consistenly associated

Язык: Английский

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Neuroimmune modulation by tryptophan derivatives in neurological and inflammatory disorders

European Journal of Cell Biology, Год журнала: 2024, Номер 103(2), С. 151418 - 151418

Опубликована: Май 8, 2024

The nervous and immune systems are highly developed, each performs specialized physiological functions. However, they work together, their dysfunction is associated with various diseases. Specialized molecules, such as neurotransmitters, cytokines, more general metabolites, essential for the appropriate regulation of both systems. Tryptophan, an amino acid, converted into functional molecules serotonin kynurenine, which play important roles in role kynurenine metabolites neurodegenerative psychiatric diseases has recently received particular attention. Recently, we found that hyperactivity pathway a critical risk factor septic shock. In this review, first outline neuroimmune interactions tryptophan derivatives then summarized changes metabolism neurological disorders. Finally, discuss potential therapeutic targets

Язык: Английский

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The tryptophan metabolic pathway of the microbiome and host cells in health and disease

International Immunology, Год журнала: 2024, Номер unknown

Опубликована: Июнь 13, 2024

Abstract The intricate and dynamic tryptophan (Trp) metabolic pathway in both the microbiome host cells highlights its profound implications for health disease. This involves complex interactions between cellular bacteria processes, producing bioactive compounds such as 5-hydroxytryptamine (5-HT) kynurenine derivatives. Immune responses to Trp metabolites through specific receptors have been explored, highlighting role of aryl hydrocarbon receptor inflammation modulation. Dysregulation this is implicated various diseases, Alzheimer’s Parkinson’s mood disorders, neuronal autoimmune diseases multiple sclerosis (MS), cancer. In article, we describe impact 5-HT, Trp, indole, on Furthermore, review microbiome-derived that affect immune contribute maintaining homeostasis, especially an experimental encephalitis model MS.

Язык: Английский

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Immunomodulatory mechanisms driving tumor escape in Glioblastoma: the central role of IDO and tryptophan metabolism in local and systemic immunotolerance

Critical Reviews in Oncology/Hematology, Год журнала: 2025, Номер unknown, С. 104657 - 104657

Опубликована: Фев. 1, 2025

Язык: Английский

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Kynurenic Acid and Promotion of Activity-Dependent Synapse Elimination in Schizophrenia

American Journal of Psychiatry, Год журнала: 2025, Номер 182(4), С. 389 - 400

Опубликована: Апрель 1, 2025

Schizophrenia is a neurodevelopmental disorder characterized by an excessive loss of synapses. Kynurenic acid (KYNA), neuroactive metabolite tryptophan along the kynurenine pathway, can induce schizophrenia-related phenotypes in rodents, and clinical studies have revealed elevated KYNA levels CNS individuals with schizophrenia. However, factors that cause schizophrenia, mechanisms which contributes to pathophysiology, remain largely elusive. The authors used patient-derived cellular modeling test hypothesis microglia-mediated synapse engulfment reducing neuronal activity. Patient-derived induced pluripotent stem cells were generate 2D cultures neurons microglia-like cells, as well forebrain organoids innately developing microglia, study how influences synaptic activity microglial uptake structures. To verify experimental data context, large-scale developmental postmortem brain tissue genetic datasets coexpression networks for KYNA-producing aminotransferases (KATs) regarding enrichment common schizophrenia risk variants functional annotations. In these models, structures inhibition endogenous production led decrease internalization synapses microglia. integrated transcriptomic showed KATs enriched genes governing Together, results link activity-dependent material while implicating pharmacological strategy avoid

Язык: Английский

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Maternal Inflammation with Elevated Kynurenine Metabolites Is Related to the Risk of Abnormal Brain Development and Behavioral Changes in Autism Spectrum Disorder

Cells, Год журнала: 2023, Номер 12(7), С. 1087 - 1087

Опубликована: Апрель 4, 2023

Several studies show that genetic and environmental factors contribute to the onset progression of neurodevelopmental disorders. Maternal immune activation (MIA) during gestation is considered one major driving this process. The kynurenine pathway (KP) a route essential amino acid L-tryptophan (Trp) catabolism in mammalian cells. Activation KP following neuro-inflammation can generate various endogenous neuroactive metabolites may impact brain functions behaviors. Additionally, neurotoxic excitotoxicity cause long-term changes trophic support, glutamatergic system, synaptic function activation. Therefore, investigating role neurodevelopment will likely promote further understanding additional pathophysiology disorders, including autism spectrum disorder (ASD). In review, we describe metabolism pregnancy represent how maternal inflammation influence development. We overview patients with ASD clinical data animal models designed verify perinatal elevation long-lasting biochemical, neuropathological, behavioral deficits later life. Our review help shed light on new therapeutic strategies interventions targeting for

Язык: Английский

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Influence of Amino Acids and Exercise on Muscle Protein Turnover, Particularly in Cancer Cachexia

Cancers, Год журнала: 2024, Номер 16(10), С. 1921 - 1921

Опубликована: Май 18, 2024

Cancer cachexia is a multifaceted syndrome that impacts individuals with advanced cancer. It causes numerous pathological changes in cancer patients, such as inflammation and metabolic dysfunction, which further diminish their quality of life. Unfortunately, also increases the risk mortality affected individuals, making it an important area focus for research treatment. Several potential nutritional therapies are being tested preclinical clinical models efficacy improving muscle metabolism patients. Despite promising results, no special have yet been validated practice. Multiple studies provide evidence benefits increasing protein synthesis through increased intake amino acids or protein. There exercise can reduce atrophy by modulating synthesis. Therefore, combination may be more effective cachexia. This review provides overview approaches use without therapy to improve

Язык: Английский

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