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
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
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
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
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.
Article
Biochemistry & Molecular Biology
Charlise Basson, June Cheptoo Serem, Yvette Nkondo Hlophe, Priyesh Bipath
Summary: The metastatic behavior of melanoma necessitates the identification of specific therapy targets. Previously, compounds L-kynurenine (L-kyn), quinolinic acid (Quin), and kynurenic acid (KA) have demonstrated antiproliferative and cytotoxic effects on cancer cells. However, their effects on melanoma have not been extensively studied. This study found that L-kyn, Quin, and KA induced cytotoxicity in B16 F10 melanoma cells, RAW 264.7 macrophage cells, and HaCat keratinocyte cells, with L-kyn being the most potent compound. In addition, L-kyn and KA induced morphological changes in all cell lines, while Quin only affected B16 F10 and RAW 264.7 cells. These results suggest that L-kyn may have potential as a treatment strategy when combined with other therapies for melanoma.
CELL BIOCHEMISTRY AND FUNCTION
(2023)
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.
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)
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)
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)
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
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
Biochemistry & Molecular Biology
Omar Taleb, Mohammed Maammar, Christian Klein, Michel Maitre, Ayikoe Guy Mensah-Nyagan
Summary: Xanthurenic acid (XA) is a metabolite of the kynurenine pathway synthesized in the brain from dietary or microbial tryptophan, suspected to modulate some pathophysiological mechanisms of neuropsychiatric and/or neurodegenerative diseases. Studies have shown that XA may play an important role in the endocrine system and could affect normal dopaminergic activity in the brain.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Review
Neurosciences
Trevor W. W. Stone, Felix I. L. Clanchy, Yi-Shu Huang, Nien-Yi Chiang, L. Gail Darlington, Richard O. O. Williams
Summary: Cytokines and kynurenine metabolites of tryptophan are two molecular families closely associated with communication between the brain and immune system. This integrated network of molecules regulates neuron and glial activity in the central nervous system and leukocyte function in the immune system, providing potential targets for the development of new treatments for disorders involving both systems.
FRONTIERS IN NEUROSCIENCE
(2022)
Article
Environmental Sciences
Farzaneh Allahdinian Hesaruiyeh, Saeed Rajabi, Mohadeseh Motamed-Jahromi, Mohammad Sarhadi, Michelle L. Bell, Razieh Khaksefidi, Somayeh Sarhadi, Leili Mohammadi, Kamal Dua, Amin Mohammadpour, Paolo Martelletti
Summary: This study aimed to evaluate the levels of lead (Pb), 8-hydroxy di-guanine (8-oxo-Gua), and malondialdehyde (MDA) in the blood serum of opium addicts and non-addicts. The results showed that the amount of Pb in the blood serum of addicts was significantly higher than non-addicts, but there were no significant differences in the levels of 8-oxo-Gua and MDA between the two groups.
INTERNATIONAL JOURNAL OF ENVIRONMENTAL RESEARCH AND PUBLIC HEALTH
(2022)
Editorial Material
Clinical Neurology
William David Wells-Gatnik, Fidel Dominique Festin Ambat, Paolo Martelletti
EXPERT REVIEW OF NEUROTHERAPEUTICS
(2022)
Article
Clinical Neurology
Claudia Altamura, R. Ornello, F. Ahmed, A. Negro, A. M. Miscio, A. Santoro, A. Alpuente, A. Russo, M. Silvestro, S. Cevoli, N. Brunelli, L. Grazzi, C. Baraldi, S. Guerzoni, A. P. Andreou, G. Lambru, I Frattale, K. Kamm, R. Ruscheweyh, M. Russo, P. Torelli, E. Filatova, N. Latysheva, A. Gryglas-Dworak, M. Straburzynski, C. Butera, B. Colombo, M. Filippi, P. Pozo-Rosich, P. Martelletti, S. Sacco, F. Vernieri
Summary: This study aimed to investigate the outcome of OnabotulinumtoxinA (OBT-A) as preventative therapy in elderly chronic migraine (CM) patients. The results showed that there were no differences in the primary and secondary endpoints between elderly and non-elderly patients in the first three treatment cycles.
JOURNAL OF NEUROLOGY
(2023)
Article
Geriatrics & Gerontology
Cristina Sanfilippo, Paola Castrogiovanni, Manlio Vinciguerra, Rosa Imbesi, Martina Ulivieri, Francesco Fazio, Kaj Blennow, Henrik Zetterberg, Michelino Di Rosa
Summary: This study found that high levels of CHI3L1 and CHI3L2 in the brains of AD patients are associated with inflammatory transcriptomic signatures. High CHI3L1 and CHI3L2 expression is associated with inflammatory features, while low expression is associated with neuronal activation. Gene ontology analysis revealed immune response as a main biological process based on the common genes regulated by the two chitinases.
Article
Geriatrics & Gerontology
Dilara Onan, William David Wells-Gatnik, Enrico Bentivegna, Christian Lampl, Paolo Martelletti
Summary: Migraine is a prevalent and burdensome disease, affecting around 14% of the global population. Recent randomized controlled trials (RCTs) of new migraine drugs have included participants aged over 65 years, providing clinicians with safety and efficacy data for treating older patients. However, the inclusion criteria of RCTs often exclude patients with multiple comorbidities, reducing the clinical applicability of the new drugs for older patients.
Article
Clinical Neurology
Dilara Onan, Ozlem Ulger, Paolo Martelletti
Summary: This study aimed to compare the effects of telerehabilitation and face-to-face rehabilitation on patients with chronic nonspecific neck pain (CNNP). The results showed that both methods were equally effective in improving neck functional capacity, reducing pain and disability.
EXPERT REVIEW OF NEUROTHERAPEUTICS
(2023)
Review
Biochemistry & Molecular Biology
Claudio Tana, David Garcia Azorin, Francesco Cinetto, Cesare Mantini, Marco Tana, Massimo Caulo, Fabrizio Ricci, Paolo Martelletti, Francesco Cipollone, Maria Adele Giamberardino
Summary: Migraine and sarcoidosis may share some common biological and clinical pathways. Both conditions involve inflammation and immune system dysregulation. Migraine is a common comorbidity in sarcoidosis patients, and there have been reports of individuals with neurosarcoidosis experiencing migraines. The exact relationship between the two disorders is still unclear.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Nutrition & Dietetics
Alessio Molfino, Giovanni Imbimbo, Maria Ida Amabile, Thomas Ammann, Luana Lionetto, Gerardo Salerno, Maurizio Simmaco, Maria Grazia Chiappini, Maurizio Muscaritoli
Summary: Fatigue is a frequent symptom in HD, and this study confirms the association between IDO activity, fatigue, and muscle mass and function in HD patients. Higher Kyn/Trp ratio and IL-6 levels were observed in fatigued patients, who also had lower muscle mass and strength.
Editorial Material
Health Care Sciences & Services
Christina Deligianni, Paolo Martelletti, Dimos D. Mitsikostas
JOURNAL OF COMPARATIVE EFFECTIVENESS RESEARCH
(2023)
Article
Clinical Neurology
Elena Gross, Elena Ruiz de la Torre, Paolo Martelletti
Summary: Despite the evidence on the epidemiology of migraine and its impact on patients in terms of disability, burden, and cost, the stigma of migraine has not been fully acknowledged as a key factor in the chronicity of the disease and social isolation of patients. In this commentary, a European advocacy body and a clinician specializing in migraine present different perspectives, highlighting the need for actions to improve community perception and propose treatment and rehabilitation paths for the reintegration of migraine sufferers into social contexts.
NEUROLOGY AND THERAPY
(2023)
Review
Biochemistry & Molecular Biology
Tsubasa Takizawa, Keiko Ihara, Shunsuke Uno, Seiya Ohtani, Narumi Watanabe, Noboru Imai, Jin Nakahara, Satoko Hori, David Garcia-Azorin, Paolo Martelletti
EXPERT OPINION ON DRUG METABOLISM & TOXICOLOGY
(2023)
Article
Pharmacology & Pharmacy
William Wells-Gatnik, Paolo Martelletti
Summary: A recent study has found an increased risk of neurodevelopmental disorders in individuals exposed to valproate or topiramate. Regulatory bodies are reviewing the safety of topiramate during pregnancy. This review highlights the concerns regarding the use of valproate and topiramate in women of childbearing potential.
EXPERT OPINION ON DRUG SAFETY
(2023)
Review
Pharmacology & Pharmacy
William David Wells-Gatnik, Tiffany Yazmin Wences Chirino, Fatma Nur Onan, Dilara Onan, Paolo Martelletti
Summary: This article introduces new drugs for the treatment of migraine and discusses their clinical trial outcomes. As approximately 50% of patients do not respond to calcitonin gene-related peptide therapies, there is significant value in future drug innovation. Overall, these emerging drugs are largely developed based on important targets of migraine pathogenesis, but the clinical value of individual drugs needs further research to appropriately target the relevant pathways.
EXPERT OPINION ON INVESTIGATIONAL DRUGS
(2023)
Article
Medicine, General & Internal
Antonio Martocchia, Cinzia Piccoli, Michele Fortunato Notarangelo, Daniela Sergi, Beata Ostrowska, Paolo Martelletti, Carmine Savoia, Luciano De Biase, Giorgio Sesti
Summary: The use of point-of-care ultrasound for evaluating left ventricle systolic function (LV EF) has shown high accuracy in this study. It can support the diagnosis of heart failure in emergency situations without delays.
INTERNAL AND EMERGENCY MEDICINE
(2023)
Article
Clinical Neurology
Arife Cimen Atalar, Ayse Nur Ozdag Acarli, Betuel Baykan, Paolo Martelletti, Hayrunnisa Bolay, Mustafa Ertas, Esme Ekizoglu, Omer Karadas, Burcu Polat, Isil Yazici Gencdal, David Garcia Azorin, Dimos Mitsikostas, Loukia Apostolakopoulou, Hamit Genc, Pinar Yalinay Dikmen, Esra Aciman Demirel, Elif Ilgaz Aydinlar, Rabia Gokcen Gozubatik-Celik, Javid Shafiyev, Bahar Tasdelen, Aynur Ozge
Summary: This multinational observational study aimed to investigate prolonged or worsened headaches associated with COVID-19 vaccination. Questionnaires were used to assess the vaccination-related headaches at three time points. Repeated K-means cluster analysis identified patient profiles with prolonged or worsened headaches related to COVID-19 vaccination.
JOURNAL OF HEADACHE AND PAIN
(2023)
