Review
Immunology
Mobina Fathi, Kimia Vakili, Shirin Yaghoobpoor, Arian Tavasol, Kimia Jazi, Ramtin Hajibeygi, Sina Shool, Fatemeh Sodeifian, Andis Klegeris, Alyssa McElhinney, Mostafa Rezaei Tavirani, Fatemeh Sayehmiri
Summary: This systematic review and meta-analysis aimed to assess the changes in kynurenine pathway metabolites in patients with neurodegenerative diseases. The results showed a significant decrease in tryptophan levels in Alzheimer's disease, Parkinson's disease, and Huntington's disease patients, along with lower levels of 3-hydroxykynurenine in AD patients and kynurenine in HD patients. These findings support the hypothesis that alterations in the kynurenine pathway may be involved in the pathogenesis of these diseases.
FRONTIERS IN IMMUNOLOGY
(2022)
Review
Immunology
Mobina Fathi, Kimia Vakili, Shirin Yaghoobpoor, Arian Tavasol, Kimia Jazi, Ashraf Mohamadkhani, Andis Klegeris, Alyssa McElhinney, Zahedeh Mafi, Mohammadreza Hajiesmaeili, Fatemeh Sayehmiri
Summary: This systematic review investigates the dysregulation of the kynurenine pathway (KP) and differences in its metabolites and enzymes in multiple sclerosis (MS) patients compared to healthy control subjects. The results suggest that alterations in KP metabolites and enzymes may be linked to MS and that certain metabolite and enzyme levels could potentially be used to differentiate between MS patients and control subjects.
FRONTIERS IN IMMUNOLOGY
(2022)
Review
Behavioral Sciences
Bing Cao, Yan Chen, Zhongyu Ren, Zihang Pan, Roger S. McIntyre, Dongfang Wang
Summary: The study explored the association between key metabolites of the KYN pathway and schizophrenia, revealing that subjects with prescribed medication had higher KYN levels, higher KYN levels in CSF, lower plasma KYN levels, and higher CSF KYNA levels were associated with SCZ, and KYN levels increased in subjects with SCZ after antipsychotic treatments.
NEUROSCIENCE AND BIOBEHAVIORAL REVIEWS
(2021)
Review
Biochemistry & Molecular Biology
Ilona Sadok, Katarzyna Jedruchniewicz
Summary: Tryptophan metabolism plays a crucial role in human health. This review provides an overview of the occurrence of tryptophan metabolites in food, analytical methods for their determination, and the fate and role of dietary tryptophan. Special attention is given to the core technique of detecting and quantifying tryptophan.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Review
Biochemical Research Methods
Takeshi Fukushima, Maho Umino, Tatsuya Sakamoto, Mayu Onozato
Summary: This review summarizes the detection of kynurenine, kynurenic acid, quinolinic acid, and other tryptophan metabolites using chromatographic methods. These metabolites have significant clinical diagnostic value for the assessment of neurological disorders.
BIOMEDICAL CHROMATOGRAPHY
(2022)
Article
Endocrinology & Metabolism
Siyu Wang, Liangshan Mu, Chunmei Zhang, Xiaoyu Long, Yurong Zhang, Rong Li, Yue Zhao, Jie Qiao
Summary: This study found that the tryptophan-kynurenine pathway was abnormally activated in patients with polycystic ovary syndrome (PCOS).
FRONTIERS IN ENDOCRINOLOGY
(2022)
Review
Microbiology
Claire Shaw, Matthias Hess, Bart C. Weimer
Summary: The gut microbiome plays a crucial role in providing the host access to otherwise indigestible nutrients and metabolizing them into bioactive components. The balance of tryptophan-derived bioactive metabolites is important for neurological homeostasis, and imbalances can contribute to neurological diseases. This narrative review focuses on the role of anthranilic acid in neurological health and disease, highlighting the contribution of the gut microbiome, the gut-brain axis, and the three major tryptophan pathways.
Article
Nutrition & Dietetics
Verena Theiler-Schwetz, Christian Trummer, Martin R. Gruebler, Martin H. Keppel, Armin Zittermann, Andreas Tomaschitz, Winfried Maerz, Andreas Meinitzer, Stefan Pilz
Summary: Accumulating evidence suggests an association of the TRP-KYN pathway with atherosclerosis and cardiovascular risk factors. Linear regression analyses showed significant associations between TRP, KYN, QUIN, and HDL, as well as smoking status and TRP/KYN pathway parameters. Further studies are needed to explore the diagnostic and therapeutic potential of the TRP-KYN pathway for cardiovascular diseases.
Article
Nutrition & Dietetics
Cezary Chojnacki, Aleksandra Blonska, Paulina Konrad, Marcin Chojnacki, Marcin Podogrocki, Tomasz Poplawski
Summary: This study aimed to evaluate the urinary excretion of selected tryptophan metabolites in patients with IBS-C and IBS-D. It was found that changes in tryptophan metabolism occurred in both groups of IBS patients compared to the control group. The 5-HIAA level was correlated with abdominal symptoms and anxiety in IBS-D patients, while the concentration of kynurenines (KYN, QA) in urine was higher in IBS-C patients and correlated with depression.
Article
Biology
Alexander Pichler, Andreas Meinitzer, Dietmar Enko, Peter Schober, Georg Singer, Christoph Castellani, Markus Herrmann, Sandra J. Holasek, Holger Till, Jana Maria Windhaber
Summary: In well-trained athletes, a significant correlation was found between TRI and maximal oxygen uptake, suggesting that TRI can be suggested as a biomarker for physical fitness.
Article
Genetics & Heredity
Cihan Yang, Chenghong Liao, Jianguo Zhao, Qingfeng Guan, Guoshun Wang, Qian Han
Summary: This study reveals the synergistic impact of alcohol and KYNA on global gene expression, specifically on gene sets related to tryptophan metabolism and cell signaling. While KYNA promotes gene expression and alcohol inhibits it, the co-intake of alcohol and KYNA leads to a stronger inhibition of overall gene expression. Tryptophan metabolism is skewed towards the kynurenine pathway and the GnRH signaling pathway is greatly enhanced. This research provides critical data to better understand the combined effects of alcohol and KYNA on human health.
Article
Psychiatry
Junchao Huang, Ping Zhang, Yanfang Zhou, Jinghui Tong, Yimin Cui, Shuping Tan, Zhiren Wang, Fude Yang, Peter Kochunov, Baopeng Tian, Li Tian, L. Elliot Hong, Yunlong Tan
Summary: The study revealed differences in TRP pathway metabolites between patients with TRS and NTRS, with the 5-HT/TRP ratio being associated with clinical symptoms and cognitive performance in TRS patients. This suggests a potential link between an upregulated 5-HT biosynthetic pathway and treatment-resistant schizophrenia, potentially leading to new pharmacological approaches for TRS.
JOURNAL OF PSYCHIATRIC RESEARCH
(2022)
Article
Nutrition & Dietetics
Cezary Chojnacki, Tomasz Poplawski, Aleksandra Blonska, Paulina Konrad, Jan Chojnacki, Janusz Blasiak
Summary: This study evaluated the efficacy of a low-FODMAP diet with a concomitant reduction in tryptophan intake for the treatment of IBS-D. The results showed that limiting tryptophan intake was more effective in improving symptoms in IBS-D patients compared to using only a low-FODMAP diet.
Article
Neurosciences
Paulo M. G. Sales, Ezra Schrage, Richard Coico, Michele Pato
Summary: This study analyzed the alterations in tryptophan catabolic pathways in mental disorders such as major depressive disorder, schizophrenia, and bipolar disorder. The results showed that patients with major depressive disorder had lower levels of tryptophan and higher activity of the catabolic pathway. Significant differences were found in schizophrenia for any of the tryptophan catabolites. Unique changes in levels of tryptophan catabolites were also observed in bipolar disorder. Furthermore, dynamic changes in cytokines and other immune/inflammatory elements played an important role in regulating the kynurenine catabolic pathway.
Article
Biochemical Research Methods
Vinod Khetarpal, Todd Herbst, Shahzad Akhtar, Amber LaFayette, Dennis Miller, James Farnham, Troy Steege, Zhixin Miao, Bryan Marks, Aaron Ledvina, Celia Dominguez
Summary: This study validated sensitive and selective LC-MS/MS methods for six kynurenine pathway metabolites in human cerebrospinal fluid and plasma. The validated methods include a four-analyte assay for simultaneous determination of kynurenine, kynurenic acid, anthranilic acid and 3-hydroxy-kynurenine, as well as separate assays for quinolinic acid and tryptophan. The use of these methods will provide reliable information in neurological diseases.
Article
Neurosciences
Judit Mally, Trevor W. Stone, Gabriella Sinko, Noerni Geisz, Elek Dinya
BRAIN RESEARCH BULLETIN
(2018)
Review
Medicine, General & Internal
Trevor W. Stone, Megan McPherson, L. Gail Darlington
Article
Oncology
Kara McNair, Caroline M. Forrest, Maria C. J. Vincenten, L. Gail Darlington, Trevor W. Stone
CANCER BIOLOGY & THERAPY
(2019)
Review
Biochemistry & Molecular Biology
Trevor W. Stone
JOURNAL OF NEUROCHEMISTRY
(2020)
Review
Geriatrics & Gerontology
Joy Ogbechi, Felix Clanchy, Yi-Shu Huang, Louise M. Topping, Trevor W. Stone, Richard O. Williams
EXPERIMENTAL GERONTOLOGY
(2020)
Review
Immunology
Yi-Shu Huang, Joy Ogbechi, Felix I. Clanchy, Richard O. Williams, Trevor W. Stone
FRONTIERS IN IMMUNOLOGY
(2020)
Review
Oncology
Trevor W. Stone
FRONTIERS IN ONCOLOGY
(2020)
Article
Neurosciences
Zsofia Halmi, Trevor W. Stone, Elek Dinya, Judit Mally
JOURNAL OF STROKE & CEREBROVASCULAR DISEASES
(2020)
Review
Clinical Neurology
Leszek Rudzki, Trevor W. Stone, Michael Maes, Blazej Misiak, Jerzy Samochowiec, Agata Szulc
Summary: B-vitamins play essential roles in central nervous system function and various psychiatric disorders, impacting glucose, fatty acid, and amino acid metabolism, as well as regulating the synthesis and metabolism of neurotransmitters and neurohormones.
PROGRESS IN NEURO-PSYCHOPHARMACOLOGY & BIOLOGICAL PSYCHIATRY
(2021)
Review
Neurosciences
Trevor W. Stone
Summary: Ionotropic glutamate receptors and nicotinic receptors for acetylcholine have interactions, including mutual regulation of subunit expression, existence of multi-functional receptor complexes, and impacts on transmitter release, cellular electrophysiology and behavior. Understanding these interactions can lead to new insights into the sites of action of glutamate and nicotinic receptor ligands for drug development.
Review
Oncology
Trevor W. Stone, Richard O. Williams
Summary: This review focuses on the role of tryptophan metabolism in inflammation and cancer development, particularly the impact of kynurenine and related compounds. It proposes targeting the kynurenine pathway to indirectly affect interacting pathways and potentially modify tryptophan metabolism. The study provides insights into the relationship between inflammation and cancer, and suggests alternative drug targets.
Review
Pharmacology & Pharmacy
Trevor W. Stone, Richard O. Williams
Summary: Lymphocytes maturing in the thymus (T cells) play a crucial role in adaptive immunity and inflammation regulation. Though the kynurenine pathway has been studied extensively in relation to its modulation of T cell function, pharmacologically manipulating this pathway did not lead to the expected therapeutic effects for autoimmune disorders and cancer. However, recent advancements in understanding the interactions between kynurenines and other pathways, as well as the development of compounds directly targeting the kynurenine pathway, have provided alternative approaches to influence T cell function.
TRENDS IN PHARMACOLOGICAL SCIENCES
(2023)
Review
Biochemistry & Molecular Biology
Trevor W. Stone, Richard O. Williams
Summary: The interaction between the central nervous system and the immune system plays a crucial role in the organism's protective reflex, with tryptophan metabolism along the kynurenine pathway being a key player.
JOURNAL OF NEUROCHEMISTRY
(2023)
Meeting Abstract
Clinical Neurology
A. Hajas, T. W. Stone, E. Dinya, J. Mally
MOVEMENT DISORDERS
(2019)
Review
Biochemistry & Molecular Biology
Trevor W. Stone, L. Gail Darlington
CELLULAR AND MOLECULAR LIFE SCIENCES
(2017)
Article
Biochemistry & Molecular Biology
Pei-Yang Gao, Ya-Nan Ou, Yi-Ming Huang, Zhi-Bo Wang, Yan Fu, Ya-Hui Ma, Qiong-Yao Li, Li-Yun Ma, Rui-Ping Cui, Yin-Chu Mi, Lan Tan, Jin-Tai Yu
Summary: Liver function may play a role in the progression of Alzheimer's disease. The study found that as AD progressed, certain liver function markers increased while others decreased. The relationship between liver function and CSF AD biomarkers indicates a potential mediation effect on cognition.
JOURNAL OF NEUROCHEMISTRY
(2024)