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Biomolecules
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Tryptophan-Kynurenine Pathway in Health and Disease
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Tryptophan-Kynurenine Pathway in Health and Disease

A special issue of Biomolecules (ISSN 2218-273X). This special issue belongs to the section "Molecular Medicine".

Deadline for manuscript submissions: closed (20 August 2024) | Viewed by 3571

Special Issue Editors

Prof. Dr. Tomasz Kocki

E-Mail Website
Guest Editor
Department of Experimental and Clinical Pharmacology, Medical University, Jaczewskiego Street 8b, 20-090 Lublin, Poland
Interests: excitotoxicity; neurodegeneration; glutamate; kynurenines; kynurenic acid
Prof. Dr. Ewa M. Urbańska

E-Mail Website
Guest Editor
Chair, Department of Experimental and Clinical Pharmacology, Medical University of Lublin, 20-090 Lublin, Poland
Interests: neurodegeneration; tryptophan metabolism; endothelium; psychiatric disorders; glutamate

Special Issue Information

Dear Colleagues,

The biological significance of tryptophan as a source of metabolites other than serotonin has garnered significant attention in recent years. The conversion of tryptophan to biologically active products occurs in various cells of vertebrates and invertebrates, including microbiota. The tryptophan derivatives kynurenines, formed along the “kynurenine pathway”, are known to integrate and modulate a plethora of physiological and pathological processes, including cellular fate, immune response or learning and memory. In consequence, the link between an imbalanced kynurenine pathway and the development of human disorders is now broadly accepted.

The aim of this Special Issue is to present novel data on the role of the tryptophan–kynurenine pathway in the development of human pathologies, with a special emphasis on the brain, cardiovascular and metabolic disorders, and the identification of novel markers and therapeutic approaches.

We encourage colleagues to submit their contributions in the form of original research papers presenting results from a broad range of in vitro and in vivo experiments, as well as from clinical studies. Timely reviews, either systematic or narrative, that present original concepts and are of interest to either broad scientific society or address highly specialized areas, are also welcome. We look forward to receiving your contributions.

Prof. Dr. Tomasz Kocki
Prof. Dr. Ewa M. Urbańska
Guest Editors

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Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Biomolecules is an international peer-reviewed open access monthly journal published by MDPI.

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Keywords

  • tryptophan
  • kynurenine pathway
  • kynurenic acid
  • neuropsychiatric disorders
  • metabolic disorders

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Published Papers (3 papers)

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Research

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19 pages, 4253 KiB  
Article
The Effects of Kynurenic Acid in Zebrafish Embryos and Adult Rainbow Trout
by Marta Marszalek-Grabska, Monika Turska-Kozlowska, Edyta Kaczorek-Lukowska, Katarzyna Wicha-Komsta, Waldemar A. Turski, Andrzej K. Siwicki and Kinga Gawel
Biomolecules 2024, 14(9), 1148; https://doi.org/10.3390/biom14091148 - 11 Sep 2024
Viewed by 799
Abstract
Kynurenic acid (KYNA) is a metabolite of tryptophan formed on the kynurenine pathway. Its pharmacological effects are relatively well characterized in mammals, whereas its role in fish is poorly understood. Therefore, the aim of the study was to expand the knowledge of KYNA’s [...] Read more.
Kynurenic acid (KYNA) is a metabolite of tryptophan formed on the kynurenine pathway. Its pharmacological effects are relatively well characterized in mammals, whereas its role in fish is poorly understood. Therefore, the aim of the study was to expand the knowledge of KYNA’s presence inside a fish’s body and its impact on fish development and function. The study was performed on zebrafish larvae and adult rainbow trout. We provide evidence that KYNA is present in the embryo, larva and mature fish and that its distribution in organs varies considerably. A study of KYNA’s effect on early larval development suggests that it can accelerate larval maturation, especially under conditions that are suboptimal for fish growth. Moreover, KYNA in concentrations over 1 mM caused morphological impairment and death of larvae. However, long-lasting exposure of larvae to subtoxic concentrations of KYNA does not affect the behavior of 5-day-old larvae kept under standard optimal conditions. We also show that ingestion of KYNA-supplemented feed can lead to KYNA accumulation, particularly in the pyloric caeca of mature trout. These results shed new light on the relevance of KYNA and provide new impulse for further research on the importance of the kynurenine pathway in fish. Full article
(This article belongs to the Special Issue Tryptophan-Kynurenine Pathway in Health and Disease)
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22 pages, 4197 KiB  
Article
Exploring the Surface: Sampling of Potential Skin Cancer Biomarkers Kynurenine and Tryptophan, Studied on 3D Melanocyte and Melanoma Models
by Sylwia Hasterok, Skaidre Jankovskaja, Ruzica Miletic Dahlström, Zdenka Prgomet, Lars Ohlsson, Sebastian Björklund and Anna Gustafsson
Biomolecules 2024, 14(7), 815; https://doi.org/10.3390/biom14070815 - 9 Jul 2024
Viewed by 1343
Abstract
Early detection of cancer via biomarkers is vital for improving patient survival rates. In the case of skin cancers, low-molecular-weight biomarkers can penetrate the skin barrier, enabling non-invasive sampling at an early stage. This study focuses on detecting tryptophan (Trp) and kynurenine (Kyn) [...] Read more.
Early detection of cancer via biomarkers is vital for improving patient survival rates. In the case of skin cancers, low-molecular-weight biomarkers can penetrate the skin barrier, enabling non-invasive sampling at an early stage. This study focuses on detecting tryptophan (Trp) and kynurenine (Kyn) on the surface of reconstructed 3D melanoma and melanocyte models. This is examined in connection with IDO-1 and IL-6 expression in response to IFN-γ or UVB stimulation, both crucial factors of the melanoma tumor microenvironment (TME). Using a polystyrene scaffold, full-thickness human skin equivalents containing fibroblasts, keratinocytes, and melanocytes or melanoma cells were developed. The samples were stimulated with IFN-γ or UVB, and Trp and Kyn secretion was measured using HPLC-PDA and HPLC-MS. The expression of IDO-1 and IL-6 was measured using RT-qPCR. Increased Trp catabolism to Kyn was observed in IFN-γ-stimulated melanoma and melanocyte models, along with higher IDO-1 expression. UVB exposure led to significant changes in Kyn levels but only in the melanoma model. This study demonstrates the potential of skin surface Trp and Kyn monitoring to capture TME metabolic changes. It also lays the groundwork for future in vivo studies, aiding in understanding and monitoring skin cancer progression. Full article
(This article belongs to the Special Issue Tryptophan-Kynurenine Pathway in Health and Disease)
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Review

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13 pages, 1504 KiB  
Review
Use of Caenorhabditis elegans to Unravel the Tripartite Interaction of Kynurenine Pathway, UPRmt and Microbiome in Parkinson’s Disease
by Charles Viau, Alyssa Nouar and Jianguo Xia
Biomolecules 2024, 14(11), 1370; https://doi.org/10.3390/biom14111370 - 28 Oct 2024
Viewed by 874
Abstract
The model organism Caenorhabditis elegans and its relationship with the gut microbiome are gaining traction, especially for the study of neurodegenerative diseases such as Parkinson’s Disease (PD). Gut microbes are known to be able to alter kynurenine metabolites in the host, directly influencing [...] Read more.
The model organism Caenorhabditis elegans and its relationship with the gut microbiome are gaining traction, especially for the study of neurodegenerative diseases such as Parkinson’s Disease (PD). Gut microbes are known to be able to alter kynurenine metabolites in the host, directly influencing innate immunity in C. elegans. While the mitochondrial unfolded protein response (UPRmt) was first characterized in C. elegans in 2007, its relevance in host–microbiome interactions has only become apparent in recent years. In this review, we provide novel insights into the current understanding of the microbiome–gut–brain axis with a focus on tripartite interactions between the UPRmt, kynurenine pathway, and microbiome in C. elegans, and explore their relationships for PD remediations. Full article
(This article belongs to the Special Issue Tryptophan-Kynurenine Pathway in Health and Disease)
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