Immune Influencers in Action: Metabolites and Enzymes of the Tryptophan-Kynurenine Metabolic Pathway

Biomedicines, Journal Year: 2021, Volume and Issue: 9(7), P. 734 - 734

Published: June 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.

Language: Английский

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Targeting gut microbiota and metabolism as the major probiotic mechanism - An evidence-based review

Trends in Food Science & Technology, Journal Year: 2023, Volume and Issue: 138, P. 178 - 198

Published: June 11, 2023

The human gut hosts complex microbial communities, which are linked to health and disease. microbiota is continuously reshaped by multiple environmental factors, especially diet. Gut dysbiosis may promote various metabolic, neurological, intestinal, cardiovascular diseases, even tumor development. Probiotics have shown promising prophylactic, mitigating, or curative effects when use as nutrient supplements adjunctive therapy. These beneficial and/or symptom alleviation often accompanied microbiome metabolome changes. Differing from other published review articles, here we summarized the latest knowledge of evidence-based health-promoting probiotics scouring literature recent animal probiotic intervention studies. To elucidate mechanisms in enhancing intestinal homeostasis, barrier function, host immunity, through modulating its metabolites. Meanwhile, also discussed challenges data analysis clinical research comparison between laboratories, provides an outlook for future perspectives applications probiotics. achieved modulation. Current discussed. Finally, provided.

Language: Английский

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Mitochondrial Impairment: A Common Motif in Neuropsychiatric Presentation? The Link to the Tryptophan–Kynurenine Metabolic System

Cells, Journal Year: 2022, Volume and Issue: 11(16), P. 2607 - 2607

Published: Aug. 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

Language: Английский

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Multifunctional nanoparticle-mediated combining therapy for human diseases

Signal Transduction and Targeted Therapy, Journal Year: 2024, Volume and Issue: 9(1)

Published: Jan. 1, 2024

Abstract Combining existing drug therapy is essential in developing new therapeutic agents disease prevention and treatment. In preclinical investigations, combined effect of certain known drugs has been well established treating extensive human diseases. Attributed to synergistic effects by targeting various pathways advantages, such as reduced administration dose, decreased toxicity, alleviated resistance, combinatorial treatment now being pursued delivering combat major clinical illnesses, cancer, atherosclerosis, pulmonary hypertension, myocarditis, rheumatoid arthritis, inflammatory bowel disease, metabolic disorders neurodegenerative Combinatorial involves combining or co-delivering two more for a specific disease. Nanoparticle (NP)-mediated delivery systems, i.e., liposomal NPs, polymeric NPs nanocrystals, are great interest wide range due targeted delivery, extended release, higher stability avoid rapid clearance at infected areas. This review summarizes targets diseases, clinically approved combinations the development multifunctional emphasizes strategies based on severe Ultimately, we discuss challenging NP-codelivery translation provide potential approaches address limitations. offers comprehensive overview recent cutting-edge NP-mediated combination

Language: Английский

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Role of Kynurenine Pathway in Oxidative Stress during Neurodegenerative Disorders

Cells, Journal Year: 2021, Volume and Issue: 10(7), P. 1603 - 1603

Published: June 26, 2021

Neurodegenerative disorders are chronic and life-threatening conditions negatively affecting the quality of patients’ lives. They often have a genetic background, but oxidative stress mitochondrial damage seem to be at least partly responsible for their development. Recent reports indicate that activation kynurenine pathway (KP), caused by an proinflammatory factors accompanying neurodegenerative processes, leads accumulation its neuroactive pro-oxidative metabolites. This increase in level, which increases damage, disrupts cellular energy metabolism. significantly reduces viability impairs proper functioning central nervous system cells may aggravate symptoms many psychiatric disorders. suggests modulation KP activity could effective alleviating these symptoms. Numerous tryptophan supplementation, inhibition enzymes, administration or analogs metabolites show promising results management animal models. review gathers systematizes knowledge concerning role enzymes development within brain during potential strategies reduce severity this process.

Language: Английский

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Neurogenic Inflammation: The Participant in Migraine and Recent Advancements in Translational Research

Biomedicines, Journal Year: 2021, Volume and Issue: 10(1), P. 76 - 76

Published: Dec. 30, 2021

Migraine is a primary headache disorder characterized by unilateral, throbbing, pulsing headache, which lasts for hours to days, and the pain can interfere with daily activities. It exhibits various symptoms, such as nausea, vomiting, sensitivity light, sound, odors, physical activity consistently contributes worsening pain. Despite intensive research, little still known about pathomechanism of migraine. widely accepted that migraine involves activation sensitization trigeminovascular system. leads release several pro-inflammatory neuropeptides neurotransmitters causes cascade inflammatory tissue responses, including vasodilation, plasma extravasation secondary capillary leakage, edema, mast cell degranulation. Convincing evidence obtained in rodent models suggests neurogenic inflammation assumed contribute development attack. Chemical stimulation dura mater triggers trigeminal system numerous molecular behavioral changes; therefore, this relevant animal model acute This narrative review discusses emerging supporting involvement pathophysiology migraine, presenting most recent advances preclinical research novel therapeutic approaches disease.

Language: Английский

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Glutamate and GABA in Microglia-Neuron Cross-Talk in Alzheimer’s Disease

International Journal of Molecular Sciences, Journal Year: 2021, Volume and Issue: 22(21), P. 11677 - 11677

Published: Oct. 28, 2021

The physiological balance between excitation and inhibition in the brain is significantly affected Alzheimer's disease (AD). Several neuroactive compounds their signaling pathways through various types of receptors are crucial homeostasis, among them glutamate γ-aminobutyric acid (GABA). Activation microglial regulates immunological response these cells, which AD could be neuroprotective or neurotoxic. novel research approaches revealed complexity function, including interplay with other cells during neuroinflammation brain. purpose this review to describe role several proteins multiple on microglia neurons, involvement a communication network that lead different metabolic loops cell death/survival. Our focused glutamatergic, GABAergic microglia-neuronal cross-talk neuroinflammation. Moreover, significance AD-related neurotoxic glutamate/GABA-mediated dialogue neurons was analyzed search targets neuroprotection, advanced pharmacological approaches.

Language: Английский

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Memory Enhancement with Kynurenic Acid and Its Mechanisms in Neurotransmission

Biomedicines, Journal Year: 2022, Volume and Issue: 10(4), P. 849 - 849

Published: April 5, 2022

Kynurenic acid (KYNA) is an endogenous tryptophan (Trp) metabolite known to possess neuroprotective property. KYNA plays critical roles in nociception, neurodegeneration, and neuroinflammation. A lower level of observed patients with neurodegenerative diseases such as Alzheimer's Parkinson's or psychiatric disorders depression autism spectrum disorders, whereas a higher associated the pathogenesis schizophrenia. Little about optimal concentration for neuroprotection threshold neurotoxicity. In this study effects on memory functions were investigated by passive avoidance test mice. Six different doses administered intracerebroventricularly previously trained CFLP mice they 24 h. High (i.e., 20-40 μg/2 μL) significantly decreased latency, low dose (0.5 elevated it compared controls, suggesting that enhanced function. Furthermore, six receptor blockers applied reveal mechanisms underlying enhancement induced KYNA. The series tests revealed possible involvement serotonergic, dopaminergic, α β adrenergic, opiate systems nootropic effect. This confirmed improved component cognitive domain, which was mediated by, at least part, four neurotransmission animal model learning memory.

Language: Английский

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Modelling the neurodevelopmental pathogenesis in neuropsychiatric disorders. Bioactive kynurenines and their analogues as neuroprotective agents—in celebration of 80th birthday of Professor Peter Riederer

Journal of Neural Transmission, Journal Year: 2022, Volume and Issue: 129(5-6), P. 627 - 642

Published: May 28, 2022

Language: Английский

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Kynurenine Pathway in Diabetes Mellitus—Novel Pharmacological Target?

Cells, Journal Year: 2023, Volume and Issue: 12(3), P. 460 - 460

Published: Jan. 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.

Language: Английский

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