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
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
Current advances in inherited cardiomyopathy
Describe in detail all novel advances in multimodality imaging related to inherited cardiomyopathy diagnosis and prognosis. Shed light to deeper phenotypic characterization. Acknowledge recent advances in genetics, genomics and precision medicineread 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
-
Effects of 8-Residue Beta Sheet Breaker Peptides on Aged Aβ40 – Induced Memory Impairment and Aβ40 Expression in Rat Brain and Serum Following Intraamygdaloid Injection
Current Alzheimer Research Emerging Role of Apelin as a Therapeutic Target in Cancer: A Patent Review
Recent Patents on Anti-Cancer Drug Discovery HSV Amplicon Vectors for Cancer Therapy
Current Gene Therapy Apoptosis in Sepsis: Mechanisms, Clinical Impact and Potential Therapeutic Targets
Current Pharmaceutical Design Regulation of Autophagy Through Multiple Independent Hypoxic Signaling Pathways
Current Molecular Medicine Snake Venom Derived Molecules in Tumor Angiogenesis and its Application in Cancer Therapy; An Overview
Current Topics in Medicinal Chemistry Molecular Targeting of Breast Cancer: Molecular Imaging and Therapy
Current Pharmaceutical Biotechnology Potential Protective Effect of Dl-3-n-butylphthalide on Chronic Cerebral Ischemia Brain Injury
CNS & Neurological Disorders - Drug Targets Targeting Antioxidants to Mitochondria: A Potential New Therapeutic Strategy for Cardiovascular Diseases
Current Pharmaceutical Design Adipose Tissue and Bone Marrow as Sources for Cell-based Therapeutic Angiogenesis in Ischemic Tissues: Biological Foundation and Clinical Prospects for Age-related Vascular Disease
Immunology, Endocrine & Metabolic Agents in Medicinal Chemistry (Discontinued) Protective Effects of Pituitary Adenylate Cyclase-Activating Polypeptide (PACAP) Against Apoptosis
Current Pharmaceutical Design Interrelationships with Metabolic Syndrome, Obesity and Cardiovascular Risk
Current Vascular Pharmacology Advances in Imaging Gene-Directed Enzyme Prodrug Therapy
Current Pharmaceutical Biotechnology Targeting Tumour Metastasis: The Emerging Role of Nanotechnology
Current Medicinal Chemistry Cellular Redox Modulator, ortho Mn(III) meso-tetrakis(N-n-Hexylpyridinium-2-yl)porphyrin, MnTnHex-2-PyP5+ in the Treatment of Brain Tumors
Anti-Cancer Agents in Medicinal Chemistry Targeting of Antioxidant and Anti-Thrombotic Drugs to Endothelial Cell Adhesion Molecules
Current Pharmaceutical Design Quantitative Proteomic Study of Peripheral Blood Monocytes Identified Novel Genes Involved in Osteoporosis
Current Proteomics Recent Patents on Live Bacteria and their Products as Potential Anticancer Agents
Recent Patents on Anti-Cancer Drug Discovery Treating Obesity: Pharmacology of Energy Expenditure
Current Drug Targets PET with Non-Standard Nuclides
Current Topics in Medicinal Chemistry