Kynurenine Pathway: A Novel Therapeutic Opportunity

A special issue of Pharmaceuticals (ISSN 1424-8247). This special issue belongs to the section "Pharmacology".

Deadline for manuscript submissions: 15 July 2024 | Viewed by 4115

Special Issue Editors

Neurobiochemistry and Behavior Laboratory, National Institute of Neurology and Neurosurgery “Manuel Velasco Suárez”, Mexico City 14269, Mexico
Interests: kynurenines and bioenergetic; tryptophan catabolism modulation; psychiatric diseases; cognition; neurodegeneration; aging
Special Issues, Collections and Topics in MDPI journals
Neurobiochemistry and Behavior Laboratory, National Institute of Neurology and Neurosurgery “Manuel Velasco Suárez”, S.S.A. Ciudad de México, Mexico
Interests: kynurenines; glial cells; psychiatric diseases; cognition; neuroimmunology; gut-brain axis
Neuroimmunology Laboratory, National Institute of Neurology and Neurosurgery “Manuel Velasco Suárez”, S.S.A. Mexico City, Mexico
Interests: kynurenine pathway; metal poisoning; neurodegenerative diseases; neurotoxicity; neurodevelopment; learning and memory

Special Issue Information

Dear Colleagues,

The understanding of tryptophan catabolism through the kynurenine pathway (KP) has advanced greatly in recent years due to new discoveries that have led to a reinterpretation of the relevance of this pathway at the physiological and pathological levels. Recent knowledge challenging the dogma of cellular distribution of the KP enzymes together with new evidence of the interconnection of kynurenines with several factors, such as the brain–gut axis, redox environment, immune modulation, and cognition reinforces the notion of KP modulation as a therapeutic target. This Special Issue of Pharmaceuticals on “Kynurenine Pathway: A Novel Therapeutic Opportunity” aims to showcase scientific advances from different fields, including basic and clinical studies focusing on the progress of research on the KP. We invite you to contribute original research articles or reviews.

Feel free to contact us if you have any questions.

We look forward to collaborating with you in this Special Issue of Pharmaceuticals.

Dr. Verónica Pérez de la Cruz
Dr. Tonali Blanco-Ayala
Dr. Daniela Ramírez-Ortega
Guest Editors

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Published Papers (3 papers)

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Research

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17 pages, 2768 KiB  
Article
Kynurenic Acid: A Novel Player in Cardioprotection against Myocardial Ischemia/Reperfusion Injuries
by Rima Kamel, Delphine Baetz, Naïg Gueguen, Lucie Lebeau, Agnès Barbelivien, Anne-Laure Guihot, Louwana Allawa, Jean Gallet, Justine Beaumont, Michel Ovize, Daniel Henrion, Pascal Reynier, Delphine Mirebeau-Prunier, Fabrice Prunier and Sophie Tamareille
Pharmaceuticals 2023, 16(10), 1381; https://doi.org/10.3390/ph16101381 - 28 Sep 2023
Cited by 1 | Viewed by 616
Abstract
Background: Myocardial infarction is one of the leading causes of mortality worldwide; hence, there is an urgent need to discover novel cardioprotective strategies. Kynurenic acid (KYNA), a metabolite of the kynurenine pathway, has been previously reported to have cardioprotective effects. However, the mechanisms [...] Read more.
Background: Myocardial infarction is one of the leading causes of mortality worldwide; hence, there is an urgent need to discover novel cardioprotective strategies. Kynurenic acid (KYNA), a metabolite of the kynurenine pathway, has been previously reported to have cardioprotective effects. However, the mechanisms by which KYNA may be protective are still unclear. The current study addressed this issue by investigating KYNA’s cardioprotective effect in the context of myocardial ischemia/reperfusion. Methods: H9C2 cells and rats were exposed to hypoxia/reoxygenation or myocardial infarction, respectively, in the presence or absence of KYNA. In vitro, cell death was quantified using flow cytometry analysis of propidium iodide staining. In vivo, TTC-Evans Blue staining was performed to evaluate infarct size. Mitochondrial respiratory chain complex activities were measured using spectrophotometry. Protein expression was evaluated by Western blot, and mRNA levels by RT-qPCR. Results: KYNA treatment significantly reduced H9C2-relative cell death as well as infarct size. KYNA did not exhibit any effect on the mitochondrial respiratory chain complex activity. SOD2 mRNA levels were increased by KYNA. A decrease in p62 protein levels together with a trend of increase in PARK2 may mark a stimulation of mitophagy. Additionally, ERK1/2, Akt, and FOXO3α phosphorylation levels were significantly reduced after the KYNA treatment. Altogether, KYNA significantly reduced myocardial ischemia/reperfusion injuries in both in vitro and in vivo models. Conclusion: Here we show that KYNA-mediated cardioprotection was associated with enhanced mitophagy and antioxidant defense. A deeper understanding of KYNA’s cardioprotective mechanisms is necessary to identify promising novel therapeutic targets and their translation into the clinical arena. Full article
(This article belongs to the Special Issue Kynurenine Pathway: A Novel Therapeutic Opportunity)
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16 pages, 3127 KiB  
Article
Kynureninase Promotes Immunosuppression and Predicts Survival in Glioma Patients: In Silico Data Analyses of the Chinese Glioma Genome Atlas (CGGA) and of the Cancer Genome Atlas (TCGA)
by Gonzalo Pérez de la Cruz, Verónica Pérez de la Cruz, Javier Navarro Cossio, Gustavo Ignacio Vázquez Cervantes, Aleli Salazar, Mario Orozco Morales and Benjamin Pineda
Pharmaceuticals 2023, 16(3), 369; https://doi.org/10.3390/ph16030369 - 28 Feb 2023
Cited by 1 | Viewed by 1797
Abstract
Kynureninase (KYNU) is a kynurenine pathway (KP) enzyme that produces metabolites with immunomodulatory properties. In recent years, overactivation of KP has been associated with poor prognosis of several types of cancer, in particular by promoting the invasion, metastasis, and chemoresistance of cancer cells. [...] Read more.
Kynureninase (KYNU) is a kynurenine pathway (KP) enzyme that produces metabolites with immunomodulatory properties. In recent years, overactivation of KP has been associated with poor prognosis of several types of cancer, in particular by promoting the invasion, metastasis, and chemoresistance of cancer cells. However, the role of KYNU in gliomas remains to be explored. In this study, we used the available data from TCGA, CGGA and GTEx projects to analyze KYNU expression in gliomas and healthy tissue, as well as the potential contribution of KYNU in the tumor immune infiltrate. In addition, immune-related genes were screened with KYNU expression. KYNU expression correlated with the increased malignancy of astrocytic tumors. Survival analysis in primary astrocytomas showed that KYNU expression correlated with poor prognosis. Additionally, KYNU expression correlated positively with several genes related to an immunosuppressive microenvironment and with the characteristic immune tumor infiltrate. These findings indicate that KYNU could be a potential therapeutic target for modulating the tumor microenvironment and enhancing an effective antitumor immune response. Full article
(This article belongs to the Special Issue Kynurenine Pathway: A Novel Therapeutic Opportunity)
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Review

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15 pages, 2335 KiB  
Review
Crosstalk between Exercise-Derived Endocannabinoidome and Kynurenines: Potential Target Therapies for Obesity and Depression Symptoms
by Tiffany Wences Chirino, Edgar Rangel López, Alexandra Luna Angulo, Paul Carrillo Mora, Carlos Landa Solis, María Alejandra Samudio Cruz, Alim C. Fuentes Bello, Rogelio Paniagua Pérez, Juan Ríos Martínez and Laura Sánchez Chapul
Pharmaceuticals 2023, 16(10), 1421; https://doi.org/10.3390/ph16101421 - 05 Oct 2023
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Abstract
The kynurenine pathway (KP) and the endocannabinoid system (ECS) are known to be deregulated in depression and obesity; however, it has been recognized that acute physical exercise has an important modulating role inducing changes in the mobilization of their respective metabolites—endocannabinoids (eCBs) and [...] Read more.
The kynurenine pathway (KP) and the endocannabinoid system (ECS) are known to be deregulated in depression and obesity; however, it has been recognized that acute physical exercise has an important modulating role inducing changes in the mobilization of their respective metabolites—endocannabinoids (eCBs) and kynurenines (KYNs)—which overlap at some points, acting as important antidepressant, anti-nociceptive, anti-inflammatory, and antioxidant biomarkers. Therefore, the aim of this review is to analyze and discuss some recently performed studies to investigate the potential interactions between both systems, particularly those related to exercise-derived endocannabinoidome and kynurenine mechanisms, and to elucidate how prescription of physical exercise could represent a new approach for the clinical management of these two conditions. Full article
(This article belongs to the Special Issue Kynurenine Pathway: A Novel Therapeutic Opportunity)
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