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)
Article
Pharmacology & Pharmacy
Soumil Dey, Aparna Banerjee Dixit, Manjari Tripathi, Ramesh Sharanappa Doddamani, Mehar Chand Sharma, Sanjeev Lalwani, Poodipedi Sarat Chandra, Jyotirmoy Banerjee
Summary: The study identified that levels of kynurenic acid were reduced and quinolinic acid levels were raised in the hippocampus of patients with MTLE-HS, along with abnormal glutamatergic activities. Altered metabolism of tryptophan-kynurenine pathway metabolites in the hippocampus could contribute to hyperglutamatergic tone in patients with MTLE-HS.
BRITISH JOURNAL OF PHARMACOLOGY
(2021)
Review
Biochemistry & Molecular Biology
Ping Chen, Xiaofei Geng
Summary: Parkinson's disease (PD) is characterized by the death of dopamine (DA) neurons and the accumulation of α-synuclein fibrils in the substantia nigra pars compacta (SNpc), along with central nervous system inflammation. Elevated levels of central inflammatory factors disrupt the kynurenine pathway (KP) in PD, leading to reduced neuroprotective metabolite KYNA and increased neurotoxic metabolite QUIN, exacerbating excitotoxicity and inflammation. KYNA analogs, precursor drugs, and KP enzyme modulators may offer potential therapeutic strategies for PD.
JOURNAL OF ENZYME INHIBITION AND MEDICINAL CHEMISTRY
(2023)
Review
Nutrition & Dietetics
Charl Alberts, Maja Owe-Larsson, Ewa M. Urbanska
Summary: Anorexia nervosa (AN) is a neuropsychiatric disorder with a high mortality rate, and current therapeutic options are unsatisfactory. The metabolism of tryptophan along the kynurenine pathway plays a crucial role in AN, and abnormalities in this pathway are associated with low body weight. Further investigation is needed to understand the effects of L-kynurenine supplementation on AN in animal models and the clinical progression of AN.
Review
Biochemistry & Molecular Biology
Tapan Behl, Ishnoor Kaur, Aayush Sehgal, Sukhbir Singh, Saurabh Bhatia, Ahmed Al-Harrasi, Gokhan Zengin, Adrian Gheorghe Bumbu, Felicia Liana Andronie-Cioara, Aurelia Cristina Nechifor, Daniela Gitea, Alexa Florina Bungau, Mirela Marioara Toma, Simona Gabriela Bungau
Summary: This article discusses the dual role of KP in Parkinson's disease and its potential role as a biomarker in PD detection, providing a basis for the development of therapeutic paradigms and targets in PD management.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Medicine, General & Internal
R. Baumgartner, M. Berg, L. Matic, K. P. Polyzos, M. J. Forteza, S. A. Hjorth, T. W. Schwartz, G. Paulson-Berne, G. K. Hansson, U. Hedin, D. F. J. Ketelhuth
Summary: The study elucidates the potential role of the kynurenine pathway in human atherosclerosis through multiplatform analysis of tissue samples. It reveals that deviation in the kynurenine pathway is associated with an increased probability of developing symptomatic unstable atherosclerotic disease, with important implications for the regulation of vascular inflammation.
JOURNAL OF INTERNAL MEDICINE
(2021)
Review
Clinical Neurology
Wenwen Ou, Yihua Chen, Yumeng Ju, Mohan Ma, Yaqi Qin, Ying Bi, Mei Liao, Bangshan Liu, Jin Liu, Yan Zhang, Lingjiang Li
Summary: This meta-analysis examined the differences in kynurenine (KYN) metabolites between patients with major depressive disorder (MDD) in the current episode and patients in remission, as well as the changes after treatments. The findings showed that during the depressive episode, patients had lower concentrations of tryptophan (TRP), KYN, kynurenic acid (KYNA), KYNA/quinolinic acid (QA), KYNA/3-hydroxykynurenine (3-HK), and KYNA/KYN, while KYN/TRP was higher. These changes were more pronounced in medication-free patients. There were no significant differences between patients in remission and healthy controls. Additionally, KYNA levels were negatively correlated with depression severity and increased significantly after treatments.
JOURNAL OF AFFECTIVE DISORDERS
(2023)
Review
Immunology
Ana Elisa Del'Arco, Deivison Silva Argolo, Gilles Guillemin, Maria de Fatima Dias Costa, Silvia Lima Costa, Alexandre Moraes Pinheiro
Summary: Neuroinflammation is a common feature in neurological disorders and can be both neuroprotective and neurotoxic. The kynurenine pathway, involved in immune regulation, neuroprotection, and neurotoxicity, is frequently activated during neuroinflammation. Studying the kynurenine pathway in the context of Neospora caninum infection can provide insights into its role in the neuroinflammatory response.
FRONTIERS IN IMMUNOLOGY
(2022)
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.
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.
Review
Cell Biology
Kamila Koziel, Ewa M. Urbanska
Summary: The tryptophan-kynurenine pathway is important for tryptophan conversion in the brain and periphery, and kynurenines have diverse biological actions. Imbalance of beneficial and harmful kynurenines is implicated in the pathogenesis of neurodegenerative and metabolic disorders including diabetes mellitus. Inflammation affects the function of the pathway, and kynurenines can modulate the immune response. This review highlights the role of the Trp-KYN pathway in diabetes and insulin resistance, suggesting it as a potential target for preventive and therapeutic interventions.
Review
Chemistry, Medicinal
Andrew Auyeung, Hank C. Wang, Kannan Aravagiri, Nebojsa Nick Knezevic
Summary: Chronic pain is a significant medical and socioeconomic issue with detrimental effects on individual patients and society. The kynurenine pathway has emerged as a potential contributor to chronic pain, with dysregulation and changes in metabolites associated with neurotoxic and inflammatory states. Further research on biomarkers and receptors involved in this pathway could lead to novel personalized treatments.
Review
Medicine, Research & Experimental
Eslam E. Abd El-Fattah
Summary: Cancer is a leading cause of death globally. The change in the tumor immune microenvironment, specifically immunosuppression, is associated with cancer progression, metastasis, recurrence, and chemoresistance. Indoleamine 2,3-dioxygenase (IDO) and its metabolite kynurenine (Kyn) play a significant role in the immunosuppression of lung cancer.
JOURNAL OF TRANSLATIONAL MEDICINE
(2022)
Article
Medical Laboratory Technology
Zahia Nadour, Christophe Simian, Olivier Laprevote, Marie-Anne Loriot, Islam Amine Larabi, Nicolas Pallet
Summary: A sensitive LC-MS/MS method was developed and validated for simultaneously determining tryptophan and ten metabolites of the kynurenine pathway in both plasma and urine. The method was used to predict acute kidney injury in patients undergoing cardiac surgery. Urinary concentrations of picolinic acid and its ratios to tryptophan and 3-hydroxy-anthranilic acid were highly predictive of AKI, suggesting picolinic acid as a potential biomarker. Monitoring kynurenine pathway activity using this method can help identify new biomarkers of kidney injury.
CLINICA CHIMICA ACTA
(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
Pharmacology & Pharmacy
Kinga Molnar, Balint Lorinczi, Csilla Fazakas, Istvan Szatmari, Ferenc Fulop, Noemi Kmetyko, Robert Berkecz, Istvan Ilisz, Istvan A. Krizbai, Imola Wilhelm, Laszlo Vecsei
Summary: The study synthesized six novel aminoalkylated amide derivatives of kynurenic acid, with SZR-104 showing the highest permeability through the blood-brain barrier. Compared to kynurenic acid, xanthurenic acid, and 39B, SZR-104 demonstrated significantly higher penetrability and potential to inhibit epileptiform activity in the brain.
Article
Clinical Neurology
Katalin Despotov, Denes Zadori, Gabor Veres, Katalin Jakab, Gabriella Gardian, Eszter Toth, Tamas Zsigmond Kincses, Laszlo Vecsei, Andras Ajtay, Daniel Bereczki, Peter Klivenyi
Summary: This study described the characteristics of Hungarian HD patients and mutation carriers, finding that the genetic and clinical features of this population were consistent with previous Hungarian studies and international literature, with the exception of a higher ratio of reduced penetrance and intermediate alleles.
Article
Clinical Neurology
Krisztian Kocsis, Nikoletta Szabo, Eszter Toth, Andras Kiraly, Peter Farago, Balint Kincses, Daniel Vereb, Bence Bozsik, Katalin Boross, Melinda Katona, Peter Bodnar, Nyul Gabor Laszlo, Laszlo Vecsei, Peter Klivenyi, Krisztina Bencsik, Zsigmond Tamas Kincses
Summary: This study demonstrates that black holes can be separated into two distinct clusters based on their intensity values on various sequences, only one of which is related to clinical parameters. It emphasizes the joint role of FSPGR and SE sequences in monitoring MS patients and provides insight into the role of black holes in MS.
FRONTIERS IN NEUROLOGY
(2021)
Article
Pharmacology & Pharmacy
Mohammad Al-Mandi Al-Karagholi, Jakob Moller Hansen, Dalia Abou-Kassem, Anna Koldbro Hansted, Kumari Ubhayasekera, Jonas Bergquist, Laszlo Vecsei, Inger Jansen-Olesen, Messoud Ashina
Summary: The kynurenine pathway is a potential drug discovery target in neuroscience, with L-kynurenine emerging as a prodrug targeting glutamate receptors. LKYN was found to be safe and well-tolerated in humans at various dose levels, with no significant vascular effects observed after infusion. Further exploration of LKYN's therapeutic potential in stroke and epilepsy in human studies is warranted.
PHARMACOLOGY RESEARCH & PERSPECTIVES
(2021)
Article
Pharmacology & Pharmacy
Masaru Tanaka, Nora Torok, Laszlo Vecsei
EXPERT OPINION ON PHARMACOTHERAPY
(2021)
Article
Biochemistry & Molecular Biology
Viktoria Kovacs, Gabor Remzso, Timea Kormoczi, Robert Berkecz, Valeria Toth-Szuki, Andrea Penzes, Laszlo Vecsei, Ferenc Domoki
Summary: The study investigated the potential neuroprotective effects of the KYNA analog SZR72 in piglets with HIE. While SZR72 enhanced neuronal activity and EEG recovery, it did not ameliorate early neuronal damage post-asphyxia. In comparison, hypothermia treatment showed the best preservation of EEG complexity, VEP, and neuronal integrity in all examined brain regions.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Clinical Neurology
Eleonora Spekker, Klaudia Flora Laborc, Zsuzsanna Bohar, Gabor Nagy-Grocz, Annamaria Fejes-Szabo, Monika Szucs, Laszlo Vecsei, Arpad Pardutz
Summary: The study found that the inflammatory soup increased the levels of certain proteins in the caudal trigeminal nucleus, which were attenuated by sumatriptan and kynurenic acid. This suggests the involvement of 5-HT1B/1D and NMDA receptors in neurogenic inflammation development and migraine attacks.
JOURNAL OF HEADACHE AND PAIN
(2021)
Editorial Material
Medicine, Research & Experimental
Masaru Tanaka, Laszlo Vecsei
Summary: The tryptophan-kynurenine metabolic pathway is crucial in producing endogenous bioactive molecules, and its activation is linked to the pathogenesis of various diseases. Efforts have been made to calibrate the levels and ratios of kynurenines to identify biomarkers and diagnostic targets. This editorial discusses the interaction between biosystems and the kynurenine system, as well as potential measures to evaluate stress levels that may lead to illnesses.
ADVANCES IN CLINICAL AND EXPERIMENTAL MEDICINE
(2021)
Article
Multidisciplinary Sciences
Rita Maszlag-Torok, Fanni A. Boros, Laszlo Vecsei, Peter Klivenyi
Summary: This study investigated the potential association of SIRT1, -2, and -6 gene polymorphisms with the risk of Parkinson's disease (PD) in the Hungarian population. It found that certain SNPs in SIRT1 and SIRT6 were weakly associated with PD risk, while SNPs in SIRT2 showed no association. Additionally, mRNA levels of SIRT1 were down-regulated, SIRT6 were up-regulated, and SIRT2 remained unchanged in PD patients compared to controls, suggesting a potential role of SIRT1 and SIRT6 in the pathogenesis of PD.
SCIENTIFIC REPORTS
(2021)
Review
Neurosciences
Daniel Pukoli, Helga Polyak, Cecilia Rajda, Laszlo Vecsei
Summary: The kynurenine pathway is involved in the pathogenesis of multiple sclerosis, with dysregulation and upregulated levels contributing to neuro-axonal damage and degeneration. Neurofilaments serve as reliable biomarkers for neuro-axonal damage severity and treatment response in multiple sclerosis. There is increasing evidence of a connection between molecules in the kynurenine metabolic pathway and changes in neurofilament concentrations, suggesting its potential as an important biomarker for disease progression.
FRONTIERS IN NEUROSCIENCE
(2021)
Article
Immunology
Marietta Z. Poles, Anna Naszai, Levente Gulacsi, Balint L. Czako, Krisztian G. Gal, Romy J. Glenz, Dishana Dookhun, Attila Rutai, Szabolcs P. Tallosy, Andrea Szabo, Balint Lorinczi, Istvan Szatmari, Ferenc Fulop, Laszlo Vecsei, Mihaly Boros, Laszlo Juhasz, Jozsef Kaszaki
Summary: KYNA and its synthetic analogues have been found to be potential neuroprotective agents in sepsis by reducing peripheral formation of NETs, lowering BBB permeability changes, and alleviating mitochondrial dysfunction in the CNS.
FRONTIERS IN IMMUNOLOGY
(2021)
Review
Biochemistry & Molecular Biology
Masaru Tanaka, Nora Torok, Fanni Toth, Agnes Szabo, Laszlo Vecsei
Summary: Chronic pain is a persistent or recurrent, unpleasant sensory and emotional experience lasting more than three months. Recent classifications by the International Association for the Study of Pain will come into effect in 2022, emphasizing neurological pathology in chronic pain while downplaying psychological or social factors. This review delves into the pain pathway, mechanisms of pain, sensitization, chronic inflammation, and the role of metabolites, exploring how psychosocial and behavioral factors contribute to the development of chronic pain.
Review
Neurosciences
Janos Tajti, Delia Szok, Aliz Nyari, Laszlo Vecsei
Summary: This review summarizes the significant breakthroughs in migraine research made by headache scientists in the past 40 years, including the pathogenesis and treatment options for migraine. The theory of the trigeminovascular system has played a crucial role in this field, and the calcitonin gene-related peptide has become an important target for the treatment of migraine. The related studies have provided a solid foundation and treatment strategies in both preclinical and clinical settings.
CNS & NEUROLOGICAL DISORDERS-DRUG TARGETS
(2022)
Review
Clinical Neurology
Masaru Tanaka, Eleonora Spekker, Agnes Szabo, Helga Polyak, Laszlo Vecsei
Summary: The neurodevelopmental theory suggests that disruptions in brain development can lead to subsequent neuropsychiatric symptoms. Preclinical studies have shown that neurodevelopmental pathology plays a role in various psychiatric disorders and neurodegenerative diseases.
JOURNAL OF NEURAL TRANSMISSION
(2022)
Article
Multidisciplinary Sciences
Helga Polyak, Edina Katalin Cseh, Zsuzsanna Bohar, Cecilia Rajda, Denes Zadori, Peter Klivenyi, Jozsef Toldi, Laszlo Vecsei
Summary: The study aimed to measure the metabolites of the KP in CPZ treated animals, with a focus on KYNA levels. Results showed a marked reduction of KYNA in the demyelinating phase, suggesting a potential involvement of the KP in the pathomechanism of MS in a non-immune mediated model.