Tryptophan metabolism as a ‘reflex’ feature of neuroimmune communication: Sensor and effector functions for the indoleamine‐2, 3‐dioxygenase kynurenine pathway DOI Creative Commons
Trevor W. Stone, Richard Williams

Journal of Neurochemistry, Год журнала: 2023, Номер unknown

Опубликована: Дек. 16, 2023

Abstract Although the central nervous system (CNS) and immune were regarded as independent entities, it is now clear that cells can influence CNS, neuroglial activity influences system. Despite many clinical implications for this ‘neuroimmune interface’, its detailed operation at molecular level remains unclear. This narrative review focuses on metabolism of tryptophan along kynurenine pathway, since products have critical actions in both systems, placing a unique position to neuroimmune communication. In particular, pathway activated by pro‐inflammatory mediators, proposed physical psychological stressors are stimuli an organismal protective reflex, with metabolites effector arm co‐ordinating neural responses. After brief interface, general perception expanded emphasize environmentally driven perspective. The initial enzymes include indoleamine‐2,3‐dioxygenase (IDO1), which induced tissue damage, inflammatory mediators or microbial products, tryptophan‐2,3‐dioxygenase (TDO), stress‐induced glucocorticoids. system, kynurenic acid modulates leucocyte differentiation, balance tolerance activating aryl hydrocarbon receptors pain via GPR35 protein. quinolinic activates N‐methyl‐D‐aspartate (NMDA)‐sensitive glutamate receptors, whereas antagonist: between glutamate, significant regulator CNS function plasticity. concept reflex coordinated protection against stress helps understand variety breadth their activity. It should also help pathological origin some psychiatric neurodegenerative diseases involving facilitating development new pharmacological strategies treatment.

Язык: Английский

Immune Influencers in Action: Metabolites and Enzymes of the Tryptophan-Kynurenine Metabolic Pathway DOI Creative Commons
Masaru Tanaka, Fanni Tóth, Helga Polyák

и другие.

Biomedicines, Год журнала: 2021, Номер 9(7), С. 734 - 734

Опубликована: Июнь 25, 2021

The tryptophan (TRP)-kynurenine (KYN) metabolic pathway is a main player of TRP metabolism through which more than 95% catabolized. activated by acute and chronic immune responses leading to wide range illnesses including cancer, diseases, neurodegenerative diseases psychiatric disorders. presence positive feedback loops facilitates amplifying the vice versa. TRP-KYN synthesizes multifarious metabolites oxidants, antioxidants, neurotoxins, neuroprotectants immunomodulators. immunomodulators are known facilitate system towards tolerogenic state, resulting in low-grade inflammation (LGI) that commonly present obesity, poor nutrition, exposer chemicals or allergens, prodromal stage various diseases. KYN, kynurenic acid, xanthurenic acid cinnabarinic aryl hydrocarbon receptor ligands serve as Furthermore, enzymes be stress hormone cortisol inflammatory cytokines, genotypic variants were observed contribute thus 2,3-dioxygenase, indoleamine 2,3-dioxygenases kynurenine-3-monooxygenase pathway. This review article discusses with special emphasis on its interaction shift LGI overviews major symptoms, pro- anti-inflammatory cytokines toxic protective KYNs explore linkage between LGI, KYNs, disorders, depressive disorder, bipolar substance use post-traumatic schizophrenia autism spectrum disorder.

Язык: Английский

Процитировано

177
Mitochondrial Impairment: A Common Motif in Neuropsychiatric Presentation? The Link to the Tryptophan–Kynurenine Metabolic System DOI Creative Commons
Masaru Tanaka, Ágnes Szabó, Eleonóra Spekker

и другие.

Cells, Год журнала: 2022, Номер 11(16), С. 2607 - 2607

Опубликована: Авг. 21, 2022

Nearly half a century has passed since the discovery of cytoplasmic inheritance human chloramphenicol resistance. The was then revealed to take place maternally by mitochondrial DNA (mtDNA). Later, number mutations in mtDNA were identified as cause severe inheritable metabolic diseases with neurological manifestation, and impairment functions been probed pathogenesis wide range illnesses including neurodegenerative diseases. Recently, growing preclinical studies have that animal behaviors are influenced possibly loss stress resilience. Indeed, high 54% patients one most common primary diseases, encephalomyopathy lactic acidosis stroke-like episodes (MELAS) syndrome, present psychiatric symptoms cognitive impairment, mood disorder, anxiety, psychosis. Mitochondria multifunctional organelles which produce cellular energy play major role other homeostasis, signaling, gene expression, among others. Mitochondrial observed be compromised become less resilient under continuous stress. Meanwhile, inflammation linked activation tryptophan (Trp)-kynurenine (KYN) system, observably contributes development pathological conditions disorders. This review discusses mitochondria Trp-KYN interaction system mitochondria, current understanding involvement clinical

Язык: Английский

Процитировано

132
Kynurenine Pathway in Diabetes Mellitus—Novel Pharmacological Target? DOI Creative Commons

Kamila Kozieł,

Ewa M. Urbańska

Cells, Год журнала: 2023, Номер 12(3), С. 460 - 460

Опубликована: Янв. 31, 2023

The tryptophan–kynurenine pathway (Trp–KYN) is the major route for tryptophan conversion in brain and periphery. Kynurenines display a wide range of biological actions (which are often contrasting) such as cytotoxic/cytoprotective, oxidant/antioxidant or pro-/anti-inflammatory. net effect depends on their local concentration, cellular environment, well complex positive negative feedback loops. imbalance between beneficial harmful kynurenines was implicated pathogenesis various neurodegenerative disorders, psychiatric illnesses metabolic including diabetes mellitus (DM). Despite available therapies, DM may lead to serious macro- microvascular complications cardio- cerebrovascular disease, peripheral vascular chronic renal diabetic retinopathy, autonomic neuropathy cognitive impairment. It established that low-grade inflammation, which coincides with DM, can affect function KP and, conversely, modulate immune response. This review provides detailed summary findings concerning status Trp–KYN based animal, human microbiome studies. We highlight importance molecular interplay deranged (functionally qualitatively) Trp development insulin resistance. emerges novel target search preventive therapeutic interventions DM.

Язык: Английский

Процитировано

61
Exploring Novel Therapeutic Targets in the Common Pathogenic Factors in Migraine and Neuropathic Pain DOI Open Access
János Tajti, Délia Szok, Anett Csáti

и другие.

International Journal of Molecular Sciences, Год журнала: 2023, Номер 24(4), С. 4114 - 4114

Опубликована: Фев. 18, 2023

Migraine and neuropathic pain (NP) are both painful, disabling, chronic conditions which exhibit some symptom similarities thus considered to share a common etiology. The calcitonin gene-related peptide (CGRP) has gained credit as target for migraine management; nevertheless, the efficacy applicability of CGRP modifiers warrant search more effective therapeutic targets management. This scoping review focuses on human studies pathogenic factors in NP, with reference available preclinical evidence explore potential novel targets. inhibitors monoclonal antibodies alleviate inflammation meninges; targeting transient receptor (TRP) ion channels may help prevent release nociceptive substances, modifying endocannabinoid system open path toward discovery analgesics. There exist tryptophan-kynurenine (KYN) metabolic system, is closely linked glutamate-induced hyperexcitability; alleviating neuroinflammation complement pain-relieving armamentarium, microglial excitation, observed conditions, be possible approach. Those several analgesic deserve explored analgesics; however, much remains missing. highlights need subtypes, TRP modulators, knowledge status KYN metabolites, consensus cytokines sampling, biomarkers function, innovative management methods NP.

Язык: Английский

Процитировано

56
Neural Correlates and Molecular Mechanisms of Memory and Learning DOI Open Access
Simone Battaglia, Alessio Avenanti, László Vécsei

и другие.

International Journal of Molecular Sciences, Год журнала: 2024, Номер 25(5), С. 2724 - 2724

Опубликована: Фев. 27, 2024

Memory and learning are essential cognitive processes that enable us to obtain, retain, recall information [...].

Язык: Английский

Процитировано

33
Neurodegeneration in Cognitive Impairment and Mood Disorders for Experimental, Clinical and Translational Neuropsychiatry DOI Creative Commons
Simone Battaglia, Alessio Avenanti, László Vécsei

и другие.

Biomedicines, Год журнала: 2024, Номер 12(3), С. 574 - 574

Опубликована: Март 5, 2024

Neurodegeneration poses a significant challenge for the fields of neuroscience and medicine, as it is underlying cause development advancement numerous neurodegenerative psychiatric disorders [...]

Язык: Английский

Процитировано

25
Innovation at the Intersection: Emerging Translational Research in Neurology and Psychiatry DOI Creative Commons
Masaru Tanaka, Simone Battaglia, Lydia Giménez‐Llort

и другие.

Cells, Год журнала: 2024, Номер 13(10), С. 790 - 790

Опубликована: Май 7, 2024

Translational research in neurological and psychiatric diseases is a rapidly advancing field that promises to redefine our approach these complex conditions [...]

Язык: Английский

Процитировано

19
Indoleamine 2, 3-dioxygenase 1 inhibition mediates the therapeutic effects in Parkinson's disease mice by modulating inflammation and neurogenesis in a gut microbiota dependent manner DOI
Chen-Meng Qiao, Xiaoyu Ma,

Lulu Tan

и другие.

Experimental Neurology, Год журнала: 2025, Номер 385, С. 115142 - 115142

Опубликована: Янв. 8, 2025

Язык: Английский

Процитировано

2
Searching for Peripheral Biomarkers in Neurodegenerative Diseases: The Tryptophan-Kynurenine Metabolic Pathway DOI Open Access
Nóra Török, Masaru Tanaka, László Vécsei

и другие.

International Journal of Molecular Sciences, Год журнала: 2020, Номер 21(24), С. 9338 - 9338

Опубликована: Дек. 8, 2020

Neurodegenerative diseases are multifactorial, initiated by a series of the causative complex which develops into certain clinical picture. The pathogenesis and disease course vary from patient to patient. Thus, it should be likewise treatment. Peripheral biomarkers play central role for tailoring personalized therapeutic plan patients who suffered neurodegenerative such as Alzheimer's disease, Parkinson's multiple sclerosis, among others. Nevertheless, use in practice is still underappreciated data presented biomarker research uncompelling, compared abundant available drug development. So case with kynurenines (KYNs) kynurenine pathway (KP) enzymes, have been associated wide range including cancer, autoimmune diseases, inflammatory neurologic psychiatric disorders. This review article discusses current knowledge KP alterations observed nervous system well periphery, its involvement progression, emerging evidence roles microbiota gut-brain axis, searching practical peripheral ensure treatment plans diseases.

Язык: Английский

Процитировано

108
Monitoring the Redox Status in Multiple Sclerosis DOI Creative Commons
Masaru Tanaka, László Vécsei

Biomedicines, Год журнала: 2020, Номер 8(10), С. 406 - 406

Опубликована: Окт. 12, 2020

Worldwide, over 2.2 million people suffer from multiple sclerosis (MS), a multifactorial demyelinating disease of the central nervous system. MS is characterized by wide range motor, autonomic, and psychobehavioral symptoms, including depression, anxiety, dementia. The blood, cerebrospinal fluid, postmortem brain samples patients provide evidence on disturbance reduction-oxidation (redox) homeostasis, such as alterations oxidative antioxidative enzyme activities presence degradation products. This review article discusses components redox reactive chemical species, enzymes, species cover frequently discussed oxygen/nitrogen infrequently featured chemicals sulfur, carbonyl, halogen, selenium, nucleophilic that potentially act reductive, well pro-oxidative stressors. systems nuclear factor erythroid-2-related 2 (NRF2)-Kelch-like ECH-associated protein 1 (KEAP1) signaling pathway. NRF2 other transcriptional factors become biomarker sensitive to initial phase stress. Altered homeostasis in were search diagnostic, prognostic, predictive, and/or therapeutic biomarker. Finally, monitoring battery products helps evaluate status expedite building personalized treatment plans for sake better quality life.

Язык: Английский

Процитировано

75