Mini Review
Volume 5 Issue 1 - 2021
Kynurenine Pathway and Human Diseases: Potential Therapeutic Agents Against Such Diseases
Chika J Mbah*
Department of Pharmaceutical and Medicinal Chemistry, Faculty of Pharmaceutical Sciences, University of Nigeria, Nsukka, Enugu State, Nigeria
*Corresponding Author: Chika J Mbah, Department of Pharmaceutical and Medicinal Chemistry, Faculty of Pharmaceutical Sciences, University of Nigeria, Nsukka, Enugu State, Nigeria.
Received: December 11, 2020; Published: December 29, 2020


Tryptophan is one of the essential amino acids. Kynurenine pathway is the major pathway in the metabolism of tryptophan. The objective of the study was to provide information on human diseases associated with kynurenine pathway as well as potential therapeutic agents that could combat such diseases.

The methodology involved gathering information from scientific journals, official books, as well the internet websites.

The results show that elevation of kynurenine‐3‐monooxygenase, quinolinic acid and 3‐hydroxykynurenine in the central nervous system leads to a number of neurological and non-neurological human diseases.

In conclusion, the study has shown that the disorder of kynurenine pathway is associated with a number of neurological and non-neurological diseases.

Keywords: Kynurenine Pathway; Human Diseases; Potential Therapeutic Agents


  1. Peters JC. “Tryptophan nutrition and metabolism: an overview”. Advances Experimental Medical Biology 294 (1991): 345-358.
  2. Guillemin GJ., et al. “Expression of indoleamine 2,3-dioxygenase and production of quinolinic acid by human microglia, astrocytes, and neurons”. Glia 49 (2009): 15-23.
  3. Lim CK., et al. “Characterization of the kynurenine pathway in human oligodendrocytes”. International Congress Series 1304 (2007): 213-217
  4. Ruddick JP., et al. “Tryptophan metabolism in the central nervous system: medical implications”. Expert Review Molecular Medicine 8(2006): 1-27.
  5. Smith JR., et al. “Kynurenine-3- monooxygenase: A review of structure, mechanism, and inhibitors”. Drug Discovery Today 21(2016) 315-324.
  6. Dang Y., et al. “Effects of oxygen on kynurenine-3-monooxygenase activity”. Redox Report 5 (2000), 81-84.
  7. Geng J and Liu A. “Heme-dependent dioxygenases in tryptophan oxidation”. Arch Biochemistry Biophysic 544 (2014): 18-26.
  8. Raison CL., et al. “CSF Concentrations of brain tryptophan and kynurenines during immune stimulation with IFN-: Relationship to CNS immune responses and depression”. Molecular Psychiatry 15 (2010): 393-403.
  9. Wilson K., et al. “Overexpression of human kynurenine-3-monooxygenase protects against 3-hydroxykynurenine-mediated apoptosis through bidirectional nonlinear feedback”. Cell Death and Disease 7 (2016): e2197.
  10. Stone TW and Darlington LG. “Endogenous kynurenines as targets for drug discovery and development”. Natural Review Drug Discovery 1 (2002): 609-620.
  11. Miller AH. “Conceptual confluence: “The kynurenine pathway as a common target for ketamine and the convergence of the inflammation and glutamate hypotheses of depression”. Neuropsychopharmacology 38 (2013): 1607-1608.
  12. Irwin MR and Miller AH. “Depressive disorders and immunity: 20 years of progress and discovery”. Brain Behav Immun 21(2007): 374-383.
  13. Beal MF., et al. “Kynurenine pathway measurements in Huntington’s disease striatum: evidence for reduced formation of kynurenic acid”. Journal of Neurochemistry 55 (1990): 1327-1339.
  14. Cherny RA., et al. “Treatment with a copper-zinc chelator markedly and rapidly inhibits beta-amyloid accumulation in Alzheimer's disease transgenic mice”. Neuron3 (2001): 665-676.
  15. Gulaj E., et al. “Kynurenine and its metabolites in Alzheimer's disease patients”. Advances in Medical Sciences 55 (2010): 204-211.
  16. Kaur DF., et al. “Genetic or pharmacological iron chelation prevents MPTPinduced neurotoxicity in vivo: a novel therapy for Parkinson's disease”. Neuron 6 (2003): 899-909.
  17. Rover SA., et al. “Synthesis and biochemical evaluation of N-(4- phenylthiazol-2-yl)benzenesulfonamides as high-affinity inhibitors of kynurenine 3-hydroxylase”. Journal Medicinal Chemistry26 (1997): 4378-4385.
  18. Nguyen T., et al. “Clioquinol down-regulates mutant huntingtin expression in vitro and mitigates pathology in a Huntington's disease mouse model”. Proceedings National Academic Sciences U S A33 (2005): 11840-11845.
  19. Beaumont V., et al. “The novel KMO inhibitor CHDI340246 leads to a restoration of electrophysiological alterations in mouse models of Huntington's disease”. Experimental Neurology 282 (2016): 99-118.
  20. Chen Y., et al. “Characterization of the kynurenine pathway in NSC-34 cell line: Implications for amyotrophic lateral sclerosis”. Journal of Neurochemistry 118 (2011): 816-825.
  21. Chen Y., et al. “The kynurenine pathway and inflammation in amyotrophic lateral sclerosis”. Neurotoxicity Research 18 (2010): 132-142.
  22. Lee JM., et al. “Involvement of quinolinic acid in the neuropathogenesis of amyotrophic lateral sclerosis”. Neuropharmacology 112 (2017): 346-364.
  23. Connick JH, et al. “Nicotinylalanine increases cerebral kynurenic acid content and has anticonvulsant activity”. General Pharmacology2(1992): 235-239.
  24. Chiarugi A and Moroni F. “Quinolinic acid formation in immune-activated mice: studies with (m-nitrobenzoyl)-alanine (mNBA) and 3,4-dimethoxy-[-N-4-(-3- nitrophenyl)thiazol-2yl]-benzenesul fonamide (Ro 61-8048), two potent and selective inhibitors of kynurenine hydroxylase”. Neuropharmacology 8 (1999): 1225-1233.
  25. Hirai K. “Dual role of the carboxyl-terminal region of pig liver l-kynurenine 3-monooxygenase: Mitochondrial-targeting signal and enzymatic activity”. Journal of Biochemistry 148 (2010): 639-650.
  26. Abdel-Magid AF. “Kynurenine monooxygenase (KMO) inhibitors for the treatment of acute pancreatitis and neurodegenerative disorders”. ACS Medicinal Chemistry Letters 6 (2015): 954-955.
  27. Skouras C., et al. “Increased levels of 3-hydroxykynurenine parallel disease severity in human acute pancreatitis”. Scientific Reports 6 (2016): 33951.
  28. Pellicciari RB., et al. “Modulation of the kynurenine pathway in search for new neuroprotective agents. Synthesis and preliminary evaluation of (mnitrobenzoyl)alanine, a potent inhibitor of kynurenine-3-hydroxylase”. Journal Medicinal Chemistry 5 (1994): 647-655.
  29. Chiarugi A. “Kynurenine 3-mono-oxygenase activity and neurotoxic kynurenine metabolites increase in the spinal cord of rats with experimental allergic encephalomyelitis”. Neuroscience 3 (2001): 687-695.
  30. Mole DJ., et al. “Kynurenine-3-monooxygenase inhibition prevents multiple organ failure in rodent models of acute pancreatitis”. Nature Medicine 22 (2016): 202-209.
  31. Jin H., et al. “Prognostic significance of kynurenine 3-monooxygenase and effects on proliferation, migration, and invasion of human hepatocellular carcinoma”. Scientific Reports 5 (2015): 10466.
  32. Isaji MH., et al. “Tranilast inhibits the proliferation, chemotaxis and tube formation of human microvascular endothelial cells in vitro and angiogenesis In vivo”. British Journal of Pharmacology6 (1997): 1061-1066.
  33. Chiu YH., et al. “Overexpression of kynurenine 3-monooxygenase correlates with cancer malignancy and predicts poor prognosis in canine mammary gland tumors”. Journal of Oncology (2019): 6201764.
  34. Muller AJ., et al. “Inhibition of indoleamine 2,3-dioxygenase, an immunoregulatory target of the cancer suppression gene Bin1, potentiates cancer chemotherapy”. Nature Medicine3 (2005): 312-319.
  35. Williamson RA., et al. “Dihydroorotate dehydrogenase is a high affinity binding protein for A77 1726 and mediator of a range of biological effects of the immunomodulatory compound”. Journal of Biology Chemistry 38 (1995): 22467-22472.
Citation: Chika J Mbah. “Kynurenine Pathway and Human Diseases: Potential Therapeutic Agents Against Such Diseases”. EC Emergency Medicine and Critical Care 5.1 (2021): 47-51.

PubMed Indexed Article

EC Pharmacology and Toxicology
LC-UV-MS and MS/MS Characterize Glutathione Reactivity with Different Isomers (2,2' and 2,4' vs. 4,4') of Methylene Diphenyl-Diisocyanate.

PMID: 31143884 [PubMed]

PMCID: PMC6536005

EC Pharmacology and Toxicology
Alzheimer's Pathogenesis, Metal-Mediated Redox Stress, and Potential Nanotheranostics.

PMID: 31565701 [PubMed]

PMCID: PMC6764777

EC Neurology
Differences in Rate of Cognitive Decline and Caregiver Burden between Alzheimer's Disease and Vascular Dementia: a Retrospective Study.

PMID: 27747317 [PubMed]

PMCID: PMC5065347

EC Pharmacology and Toxicology
Will Blockchain Technology Transform Healthcare and Biomedical Sciences?

PMID: 31460519 [PubMed]

PMCID: PMC6711478

EC Pharmacology and Toxicology
Is it a Prime Time for AI-powered Virtual Drug Screening?

PMID: 30215059 [PubMed]

PMCID: PMC6133253

EC Psychology and Psychiatry
Analysis of Evidence for the Combination of Pro-dopamine Regulator (KB220PAM) and Naltrexone to Prevent Opioid Use Disorder Relapse.

PMID: 30417173 [PubMed]

PMCID: PMC6226033

EC Anaesthesia
Arrest Under Anesthesia - What was the Culprit? A Case Report.

PMID: 30264037 [PubMed]

PMCID: PMC6155992

EC Orthopaedics
Distraction Implantation. A New Technique in Total Joint Arthroplasty and Direct Skeletal Attachment.

PMID: 30198026 [PubMed]

PMCID: PMC6124505

EC Pulmonology and Respiratory Medicine
Prevalence and factors associated with self-reported chronic obstructive pulmonary disease among adults aged 40-79: the National Health and Nutrition Examination Survey (NHANES) 2007-2012.

PMID: 30294723 [PubMed]

PMCID: PMC6169793

EC Dental Science
Important Dental Fiber-Reinforced Composite Molding Compound Breakthroughs

PMID: 29285526 [PubMed]

PMCID: PMC5743211

EC Microbiology
Prevalence of Intestinal Parasites Among HIV Infected and HIV Uninfected Patients Treated at the 1o De Maio Health Centre in Maputo, Mozambique

PMID: 29911204 [PubMed]

PMCID: PMC5999047

EC Microbiology
Macrophages and the Viral Dissemination Super Highway

PMID: 26949751 [PubMed]

PMCID: PMC4774560

EC Microbiology
The Microbiome, Antibiotics, and Health of the Pediatric Population.

PMID: 27390782 [PubMed]

PMCID: PMC4933318

EC Microbiology
Reactive Oxygen Species in HIV Infection

PMID: 28580453 [PubMed]

PMCID: PMC5450819

EC Microbiology
A Review of the CD4 T Cell Contribution to Lung Infection, Inflammation and Repair with a Focus on Wheeze and Asthma in the Pediatric Population

PMID: 26280024 [PubMed]

PMCID: PMC4533840

EC Neurology
Identifying Key Symptoms Differentiating Myalgic Encephalomyelitis and Chronic Fatigue Syndrome from Multiple Sclerosis

PMID: 28066845 [PubMed]

PMCID: PMC5214344

EC Pharmacology and Toxicology
Paradigm Shift is the Normal State of Pharmacology

PMID: 28936490 [PubMed]

PMCID: PMC5604476

EC Neurology
Examining those Meeting IOM Criteria Versus IOM Plus Fibromyalgia

PMID: 28713879 [PubMed]

PMCID: PMC5510658

EC Neurology
Unilateral Frontosphenoid Craniosynostosis: Case Report and a Review of the Literature

PMID: 28133641 [PubMed]

PMCID: PMC5267489

EC Ophthalmology
OCT-Angiography for Non-Invasive Monitoring of Neuronal and Vascular Structure in Mouse Retina: Implication for Characterization of Retinal Neurovascular Coupling

PMID: 29333536 [PubMed]

PMCID: PMC5766278

EC Neurology
Longer Duration of Downslope Treadmill Walking Induces Depression of H-Reflexes Measured during Standing and Walking.

PMID: 31032493 [PubMed]

PMCID: PMC6483108

EC Microbiology
Onchocerciasis in Mozambique: An Unknown Condition for Health Professionals.

PMID: 30957099 [PubMed]

PMCID: PMC6448571

EC Nutrition
Food Insecurity among Households with and without Podoconiosis in East and West Gojjam, Ethiopia.

PMID: 30101228 [PubMed]

PMCID: PMC6086333

EC Ophthalmology
REVIEW. +2 to +3 D. Reading Glasses to Prevent Myopia.

PMID: 31080964 [PubMed]

PMCID: PMC6508883

EC Gynaecology
Biomechanical Mapping of the Female Pelvic Floor: Uterine Prolapse Versus Normal Conditions.

PMID: 31093608 [PubMed]

PMCID: PMC6513001

EC Dental Science
Fiber-Reinforced Composites: A Breakthrough in Practical Clinical Applications with Advanced Wear Resistance for Dental Materials.

PMID: 31552397 [PubMed]

PMCID: PMC6758937

EC Microbiology
Neurocysticercosis in Child Bearing Women: An Overlooked Condition in Mozambique and a Potentially Missed Diagnosis in Women Presenting with Eclampsia.

PMID: 31681909 [PubMed]

PMCID: PMC6824723

EC Microbiology
Molecular Detection of Leptospira spp. in Rodents Trapped in the Mozambique Island City, Nampula Province, Mozambique.

PMID: 31681910 [PubMed]

PMCID: PMC6824726

EC Neurology
Endoplasmic Reticulum-Mitochondrial Cross-Talk in Neurodegenerative and Eye Diseases.

PMID: 31528859 [PubMed]

PMCID: PMC6746603

EC Psychology and Psychiatry
Can Chronic Consumption of Caffeine by Increasing D2/D3 Receptors Offer Benefit to Carriers of the DRD2 A1 Allele in Cocaine Abuse?

PMID: 31276119 [PubMed]

PMCID: PMC6604646

EC Anaesthesia
Real Time Locating Systems and sustainability of Perioperative Efficiency of Anesthesiologists.

PMID: 31406965 [PubMed]

PMCID: PMC6690616

EC Pharmacology and Toxicology
A Pilot STEM Curriculum Designed to Teach High School Students Concepts in Biochemical Engineering and Pharmacology.

PMID: 31517314 [PubMed]

PMCID: PMC6741290

EC Pharmacology and Toxicology
Toxic Mechanisms Underlying Motor Activity Changes Induced by a Mixture of Lead, Arsenic and Manganese.

PMID: 31633124 [PubMed]

PMCID: PMC6800226

EC Neurology
Research Volunteers' Attitudes Toward Chronic Fatigue Syndrome and Myalgic Encephalomyelitis.

PMID: 29662969 [PubMed]

PMCID: PMC5898812

EC Pharmacology and Toxicology
Hyperbaric Oxygen Therapy for Alzheimer's Disease.

PMID: 30215058 [PubMed]

PMCID: PMC6133268

News and Events

October Issue Release

We always feel pleasure to share our updates with you all. Here, notifying you that we have successfully released the October issue of respective journals and the latest articles can be viewed on the current issue pages.

Submission Deadline for Upcoming Issue

Ecronicon delightfully welcomes all the authors around the globe for effective collaboration with an article submission for the upcoming issue of respective journals. Submissions are accepted on/before November 04, 2021.

Certificate of Publication

Ecronicon honors with a "Publication Certificate" to the corresponding author by including the names of co-authors as a token of appreciation for publishing the work with our respective journals.

Best Article of the Issue

Editors of respective journals will always be very much interested in electing one Best Article after each issue release. The authors of the selected article will be honored with a "Best Article of the Issue" certificate.

Certifying for Review

Ecronicon certifies the Editors for their first review done towards the assigned article of the respective journals.

Latest Articles

The latest articles will be updated immediately on the articles in press page of the respective journals.

Immediate Assistance

The prime motto of this team is to clarify all the queries without any delay or hesitation to avoid the inconvenience. For immediate assistance on your queries please don't hesitate to drop an email to