Abstract
The disturbance of the dopaminergic neurotransmission is a key-feature in the neurobiology of schizophrenia. The interaction between the dopaminergic and the glutamatergic neurotransmission, however, attracted more notice to the glutamatergic system. Recent research focussed on factors influencing the glutamatergic neurotransmission. A pro-inflammatory immune state influences the glutamatergic neurotransmission indirectly by its effects on the tryptophan/kynurenine metabolism. The immune response in schizophrenia seems to be associated with the activation of the enzyme indoleamine 2,3-dioxygenase (IDO) and imbalance in the tryptophan/kynurenine metabolism resulting in increased production of kynurenic acid in the brain. This is associated with an imbalance in the glutamatergic neurotransmission, leading to an NMDA antagonism in schizophrenia. The immunological effects of antipsychotics reverse partly the immune imbalance and the unphysiologically enhanced production of the kynurenic acid. These immunological and neurochemical imbalances result in a chronic pro-inflammatory state in association with increased prostaglandin E2 (PGE2) production, increased cyclo-oxygenase-2 (COX-2) expression and increased pro-inflammatory cytokines production and NMDA receptor hypofunctioning. Substances acting directly on the kynurenine metabolism are still in very early stages of development, anti-inflammatory drugs acting indirectly on this metabolism are discussed as therapeutic or preventive agents in schizophrenia. Most of the existing data are related to COX-2 inhibitors, which have been tested in animal experiments and in clinical trials, pointing to favourable effects in schizophrenia.
Keywords: Schizophrenia, tryptophan, kynurenine, immune system psychoneuroimmunology
Current Pharmaceutical Design
Title: Kynurenine Pathway in Schizophrenia: Pathophysiological and Therapeutic Aspects
Volume: 17 Issue: 2
Author(s): Norbert Muller, Aye-Mu Myint and Markus J. Schwarz
Affiliation:
Keywords: Schizophrenia, tryptophan, kynurenine, immune system psychoneuroimmunology
Abstract: The disturbance of the dopaminergic neurotransmission is a key-feature in the neurobiology of schizophrenia. The interaction between the dopaminergic and the glutamatergic neurotransmission, however, attracted more notice to the glutamatergic system. Recent research focussed on factors influencing the glutamatergic neurotransmission. A pro-inflammatory immune state influences the glutamatergic neurotransmission indirectly by its effects on the tryptophan/kynurenine metabolism. The immune response in schizophrenia seems to be associated with the activation of the enzyme indoleamine 2,3-dioxygenase (IDO) and imbalance in the tryptophan/kynurenine metabolism resulting in increased production of kynurenic acid in the brain. This is associated with an imbalance in the glutamatergic neurotransmission, leading to an NMDA antagonism in schizophrenia. The immunological effects of antipsychotics reverse partly the immune imbalance and the unphysiologically enhanced production of the kynurenic acid. These immunological and neurochemical imbalances result in a chronic pro-inflammatory state in association with increased prostaglandin E2 (PGE2) production, increased cyclo-oxygenase-2 (COX-2) expression and increased pro-inflammatory cytokines production and NMDA receptor hypofunctioning. Substances acting directly on the kynurenine metabolism are still in very early stages of development, anti-inflammatory drugs acting indirectly on this metabolism are discussed as therapeutic or preventive agents in schizophrenia. Most of the existing data are related to COX-2 inhibitors, which have been tested in animal experiments and in clinical trials, pointing to favourable effects in schizophrenia.
Export Options
About this article
Cite this article as:
Muller Norbert, Myint Aye-Mu and J. Schwarz Markus, Kynurenine Pathway in Schizophrenia: Pathophysiological and Therapeutic Aspects, Current Pharmaceutical Design 2011; 17 (2) . https://dx.doi.org/10.2174/138161211795049552
DOI https://dx.doi.org/10.2174/138161211795049552 |
Print ISSN 1381-6128 |
Publisher Name Bentham Science Publisher |
Online ISSN 1873-4286 |
Call for Papers in Thematic Issues
"Tuberculosis Prevention, Diagnosis and Drug Discovery"
The Nobel Prize-winning discoveries of Mycobacterium tuberculosis and streptomycin have enabled an appropriate diagnosis and an effective treatment of tuberculosis (TB). Since then, many newer diagnosis methods and drugs have been saving millions of lives. Despite advances in the past, TB is still a leading cause of infectious disease mortality ...read more
Current Pharmaceutical challenges in the treatment and diagnosis of neurological dysfunctions
Neurological dysfunctions (MND, ALS, MS, PD, AD, HD, ALS, Autism, OCD etc..) present significant challenges in both diagnosis and treatment, often necessitating innovative approaches and therapeutic interventions. This thematic issue aims to explore the current pharmaceutical landscape surrounding neurological disorders, shedding light on the challenges faced by researchers, clinicians, and ...read more
Emerging and re-emerging diseases
Faced with a possible endemic situation of COVID-19, the world has experienced two important phenomena, the emergence of new infectious diseases and/or the resurgence of previously eradicated infectious diseases. Furthermore, the geographic distribution of such diseases has also undergone changes. This context, in turn, may have a strong relationship with ...read more
Melanoma and Non-Melanoma Skin Cancer Treatment: Standard of Care and Recent Advances
In this thematic issue, we aim to provide a standard of care of the diagnosis and treatment of melanoma and non-melanoma skin cancer. The editor will invite authors from different countries who will write review articles of melanoma and non-melanoma skin cancers. The Diagnosis, Staging, Surgical Treatment, Non-Surgical Treatment all ...read more
- Author Guidelines
- Graphical Abstracts
- Fabricating and Stating False Information
- Research Misconduct
- Post Publication Discussions and Corrections
- Publishing Ethics and Rectitude
- Increase Visibility of Your Article
- Archiving Policies
- Peer Review Workflow
- Order Your Article Before Print
- Promote Your Article
- Manuscript Transfer Facility
- Editorial Policies
- Allegations from Whistleblowers
- Announcements
Related Articles
-
The RNA-Dependent-RNA Polymerase, an Emerging Antiviral Drug Target for the Hendra Virus
Current Drug Targets Viruses and Multiple Sclerosis
CNS & Neurological Disorders - Drug Targets Effects of Vitamin A Deficiency and Opioids on Parvalbumin + Interneurons in the Hippocampus of the HIV-1 Transgenic Rat
Current HIV Research Astragaloside IV Supplementation Promotes A Neuroprotective Effect in Experimental Models of Neurological Disorders: A Systematic Review
Current Neuropharmacology Sex Steroids in Autoimmune Diseases
Current Topics in Medicinal Chemistry Using Non-Pharmacological Approaches for CJD Patient and Family Support as Provided by the CJD Foundation and CJD Insight
CNS & Neurological Disorders - Drug Targets Functional Immunoregulation by Heme Oxygenase 1 in Juvenile Autoimmune Diseases
Current Gene Therapy Erythropoietin and Wnt1 Govern Pathways of mTOR, Apaf-1, and XIAP in Inflammatory Microglia
Current Neurovascular Research Clinical Use of Rituximab in Patients with HIV Related Lymphoma and Multicentric Castlemans Disease
Current Drug Delivery The Contribution of γδ T Cells to the Pathogenesis of EAE and MS
Current Molecular Medicine Development of Nucleic Acid Drugs for Neurological Disorders
Current Topics in Medicinal Chemistry Agonists of the Tissue-Protective Erythropoietin Receptor in the Treatment of Parkinson’s Disease
Current Topics in Medicinal Chemistry Potential Control of Multiple Sclerosis by Cannabis and the Endocannabinoid System
CNS & Neurological Disorders - Drug Targets Simultaneous HPLC Determination of Metronidazole and Spiramycin in Plasma and Brain of Mouse
Current Pharmaceutical Analysis The Non-Canonical IκB Kinases IKKε and TBK1 as Potential Targets for the Development of Novel Therapeutic Drugs
Current Molecular Medicine Use of Fusion Proteins and Procaryotic Display Systems for Delivery of HIV-1 Antigens: Development of Novel Vaccines for HIV-1 Infection
Current HIV Research Editorial [Hot Topic: Protein Peptide Informatics and Drug Designing - Some Computational Techniques for Structural Genomics Based Approaches (Part II) (Guest Editor: Rajani R. Joshi)]
Protein & Peptide Letters Immunopotentiation for Bacterial Biodefense
Current Topics in Medicinal Chemistry The Role of Vasopressin in Affective Disorders: Possible Targets of Intervention
Central Nervous System Agents in Medicinal Chemistry Natural Products: A Rich Source of Antiviral Drug Lead Candidates for the Management of COVID-19
Current Pharmaceutical Design