Abstract
The tripeptide, glutathione (γ-glutamylcysteinylglycine) is the primary endogenous free radical scavenger in the human body. When glutathione (GSH) levels are reduced there is an increased potential for cellular oxidative stress, characterised by an increase and accruement of reactive oxygen species (ROS). Oxidative stress has been implicated in the pathology of schizophrenia and bipolar disorder. This could partly be caused by alterations in dopaminergic and glutamatergic activity that are implicated in these illnesses. Glutamate and dopamine are highly redox reactive molecules and produce ROS during normal neurotransmission. Alterations to these neurotransmitter pathways may therefore increase the oxidative burden in the brain. Furthermore, mitochondrial dysfunction, as a source of oxidative stress, has been documented in both schizophrenia and bipolar disorder. The combination of altered neurotransmission and this mitochondrial dysfunction leading to oxidative damage may ultimately contribute to illness symptoms. Animal models have been established to investigate the involvement of glutathione depletion in aspects of schizophrenia and bipolar disorder to further characterise the role of oxidative stress in psychopathology. Stemming from preclinical evidence, clinical studies have recently shown antioxidant precursor treatment to be effective in schizophrenia and bipolar disorder, providing a novel clinical angle to augment often suboptimal conventional treatments.
Keywords: Glutathione, N-acetyl cysteine, oxidative stress, schizophrenia, mania, depression, bipolar disorder, animal models
Current Medicinal Chemistry
Title: A Role for Glutathione in the Pathophysiology of Bipolar Disorder and Schizophrenia? Animal Models and Relevance to Clinical Practice
Volume: 16 Issue: 23
Author(s): O. M. Dean, M. van den Buuse, A.I. Bush, D.L. Copolov, F. Ng, S. Dodd and M. Berk
Affiliation:
Keywords: Glutathione, N-acetyl cysteine, oxidative stress, schizophrenia, mania, depression, bipolar disorder, animal models
Abstract: The tripeptide, glutathione (γ-glutamylcysteinylglycine) is the primary endogenous free radical scavenger in the human body. When glutathione (GSH) levels are reduced there is an increased potential for cellular oxidative stress, characterised by an increase and accruement of reactive oxygen species (ROS). Oxidative stress has been implicated in the pathology of schizophrenia and bipolar disorder. This could partly be caused by alterations in dopaminergic and glutamatergic activity that are implicated in these illnesses. Glutamate and dopamine are highly redox reactive molecules and produce ROS during normal neurotransmission. Alterations to these neurotransmitter pathways may therefore increase the oxidative burden in the brain. Furthermore, mitochondrial dysfunction, as a source of oxidative stress, has been documented in both schizophrenia and bipolar disorder. The combination of altered neurotransmission and this mitochondrial dysfunction leading to oxidative damage may ultimately contribute to illness symptoms. Animal models have been established to investigate the involvement of glutathione depletion in aspects of schizophrenia and bipolar disorder to further characterise the role of oxidative stress in psychopathology. Stemming from preclinical evidence, clinical studies have recently shown antioxidant precursor treatment to be effective in schizophrenia and bipolar disorder, providing a novel clinical angle to augment often suboptimal conventional treatments.
Export Options
About this article
Cite this article as:
Dean M. O., den Buuse van M., Bush A.I., Copolov D.L., Ng F., Dodd S. and Berk M., A Role for Glutathione in the Pathophysiology of Bipolar Disorder and Schizophrenia? Animal Models and Relevance to Clinical Practice, Current Medicinal Chemistry 2009; 16 (23) . https://dx.doi.org/10.2174/092986709788803060
DOI https://dx.doi.org/10.2174/092986709788803060 |
Print ISSN 0929-8673 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-533X |
Call for Papers in Thematic Issues
Advances in Medicinal Chemistry: From Cancer to Chronic Diseases.
The broad spectrum of the issue will provide a comprehensive overview of emerging trends, novel therapeutic interventions, and translational insights that impact modern medicine. The primary focus will be diseases of global concern, including cancer, chronic pain, metabolic disorders, and autoimmune conditions, providing a broad overview of the advancements in ...read more
Approaches to the treatment of chronic inflammation
Chronic inflammation is a hallmark of numerous diseases, significantly impacting global health. Although chronic inflammation is a hot topic, not much has been written about approaches to its treatment. This thematic issue aims to showcase the latest advancements in chronic inflammation treatment and foster discussion on future directions in this ...read more
Cellular and Molecular Mechanisms of Non-Infectious Inflammatory Diseases: Focus on Clinical Implications
The Special Issue covers the results of the studies on cellular and molecular mechanisms of non-infectious inflammatory diseases, in particular, autoimmune rheumatic diseases, atherosclerotic cardiovascular disease and other age-related disorders such as type II diabetes, cancer, neurodegenerative disorders, etc. Review and research articles as well as methodology papers that summarize ...read more
Chalcogen-modified nucleic acid analogues
Chalcogen-modified nucleosides, nucleotides and oligonucleotides have been of great interest to scientific research for many years. The replacement of oxygen in the nucleobase, sugar or phosphate backbone by chalcogen atoms (sulfur, selenium, tellurium) gives these biomolecules unique properties resulting from their altered physical and chemical properties. The continuing interest in ...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
-
Chemoprevention Gene Therapy (CGT) of Pancreatic Cancer Using Perillyl Alcohol and a Novel Chimeric Serotype Cancer Terminator Virus
Current Molecular Medicine The Plasma Levels of hsa-miR-19b-3p, hsa-miR-125b-5p, and hsamiR- 320c in Patients with Asthma, COPD and Asthma-COPD Overlap Syndrome (ACOS)
MicroRNA Novel Approaches for Molecular Targeted Therapy of Breast Cancer: Interfering with PI3K/AKT/mTOR Signaling
Current Cancer Drug Targets Store-Dependent Ca2+ Entry in Endothelial Progenitor Cells As a Perspective Tool to Enhance Cell-Based Therapy and Adverse Tumour Vascularization
Current Medicinal Chemistry Chinese Medicinal Herbs as Source of Antioxidant Compounds – Where Tradition Meets the Future
Current Medicinal Chemistry Perioperative Heart-Brain Axis Protection in Obese Surgical Patients: The Nutrigenomic Approach
Current Medicinal Chemistry Nitric Oxide and Dietary Factors: Part II Cholesterol, Fat, Amino Acids,Proteins and Carbohydrate
Vascular Disease Prevention (Discontinued) Rational Combination of Targeted Therapies As A Strategy to Overcome The Mechanisms of Resistance to Inhibitors of EGFR Signaling
Current Pharmaceutical Design Potential Control of Multiple Sclerosis by Cannabis and the Endocannabinoid System
CNS & Neurological Disorders - Drug Targets Looking Beyond Inhibition of VEGF/mTOR: Emerging Targets for Renal Cell Carcinoma Drug Development
Current Clinical Pharmacology Heterocyclic Drug-polymer Conjugates for Cancer Targeted Drug Delivery
Anti-Cancer Agents in Medicinal Chemistry Autophagy Regulators as Potential Cancer Therapeutic agents: A Review
Current Topics in Medicinal Chemistry Glia: An Important Target for Anti-Inflammatory and Antidepressant Activity
Current Drug Targets Targeting Apoptotic Pathways in Myocardial Infarction: Attenuated by Phytochemicals
Cardiovascular & Hematological Agents in Medicinal Chemistry Renal Cell Cancer and Positron Emission Tomography- an Evolving Diagnostic and Therapeutic Relationship
Current Medical Imaging Neuroprotective Activities of Orientin: A Review
Current Traditional Medicine New Achievements in Bioinformatics Prediction of Post Translational Modification of Proteins
Current Topics in Medicinal Chemistry Hypoxia Inducible Factor-1 as a Therapeutic Target in Cerebral Ischemia
Current Signal Transduction Therapy From A1 to A3 en passant Through A2A Receptors in the Hippocampus: Pharmacological Implications
CNS & Neurological Disorders - Drug Targets Cytokine-Purine Interactions in Traumatic Stress, Behavioral Depression,and Sickness
CNS & Neurological Disorders - Drug Targets