Abstract
Bipolar Disorder (BD) is characterized by recurring mood swings, which are not completely understood yet. So far, it is an accepted theory that multiple factors contribute to pathogenesis of BD according to the vulnerability-stressmodel. This model combines on the one hand biological predisposing vulnerability, and on the other hand several chronic and acute stressful negative events as underlying mechanisms of BD. Recently, ER (Endoplasmic Reticulum) stress reached the spotlight of BD research again. The expression of the chaperone BiP (syn. GRP78/glucose-regulated protein, 78kDa), which is highly expressed in the Endoplasmic Reticulum (ER), is upregulated by different kinds of mood stabilizers. These results implied that the ER, an organelle which is prone towards different kinds of cellular stress, might be involved in the pathophysiology of BD. This hypothesis was further strengthened by hypothesis driven genetic association studies, which showed significant association of BiP promotor polymorphisms with BD. Also other ER-stress associated genes like XBP1 (X-box binding protein 1) or GRP94 (glucose-regulated protein, 94kDa, synonym for heat shock protein HSP90B1) were recently linked to BD in hypothesis driven gene association studies. In addition to the proteins mentioned before, our review focuses on further UPR (Unfolded Protein Response) related proteins associated with BD and raises the hypothesis that ER-stress may represent a common interface between BD and obesity which is overrepresented in BD patients. Finally, members of the UPR pathway are discussed as putative targets for mood stabilizers.
Keywords: Bipolar disorder, endoplasmic reticulum, endoplasmic reticulum stress, unfolded protein response, lithium, valproate.
CNS & Neurological Disorders - Drug Targets
Title:Endoplasmic Reticulum Stress and Bipolar Disorder - Almost Forgotten Therapeutic Drug Targets in the Unfolded Protein Response Pathway Revisited
Volume: 15 Issue: 4
Author(s): Susanne A. Bengesser, Robert Fuchs, Nina Lackner, Armin Birner, Bernd Reininghaus, Nathalie Meier-Allard, Anika Stracke, Hans-Peter Kapfhammer, Eva Z. Reininghaus and Sandra Wallner-Liebmann
Affiliation:
Keywords: Bipolar disorder, endoplasmic reticulum, endoplasmic reticulum stress, unfolded protein response, lithium, valproate.
Abstract: Bipolar Disorder (BD) is characterized by recurring mood swings, which are not completely understood yet. So far, it is an accepted theory that multiple factors contribute to pathogenesis of BD according to the vulnerability-stressmodel. This model combines on the one hand biological predisposing vulnerability, and on the other hand several chronic and acute stressful negative events as underlying mechanisms of BD. Recently, ER (Endoplasmic Reticulum) stress reached the spotlight of BD research again. The expression of the chaperone BiP (syn. GRP78/glucose-regulated protein, 78kDa), which is highly expressed in the Endoplasmic Reticulum (ER), is upregulated by different kinds of mood stabilizers. These results implied that the ER, an organelle which is prone towards different kinds of cellular stress, might be involved in the pathophysiology of BD. This hypothesis was further strengthened by hypothesis driven genetic association studies, which showed significant association of BiP promotor polymorphisms with BD. Also other ER-stress associated genes like XBP1 (X-box binding protein 1) or GRP94 (glucose-regulated protein, 94kDa, synonym for heat shock protein HSP90B1) were recently linked to BD in hypothesis driven gene association studies. In addition to the proteins mentioned before, our review focuses on further UPR (Unfolded Protein Response) related proteins associated with BD and raises the hypothesis that ER-stress may represent a common interface between BD and obesity which is overrepresented in BD patients. Finally, members of the UPR pathway are discussed as putative targets for mood stabilizers.
Export Options
About this article
Cite this article as:
Bengesser A. Susanne, Fuchs Robert, Lackner Nina, Birner Armin, Reininghaus Bernd, Meier-Allard Nathalie, Stracke Anika, Kapfhammer Hans-Peter, Reininghaus Z. Eva and Wallner-Liebmann Sandra, Endoplasmic Reticulum Stress and Bipolar Disorder - Almost Forgotten Therapeutic Drug Targets in the Unfolded Protein Response Pathway Revisited, CNS & Neurological Disorders - Drug Targets 2016; 15 (4) . https://dx.doi.org/10.2174/1871527315666160321104613
DOI https://dx.doi.org/10.2174/1871527315666160321104613 |
Print ISSN 1871-5273 |
Publisher Name Bentham Science Publisher |
Online ISSN 1996-3181 |
Call for Papers in Thematic Issues
Diagnosis and treatment of central nervous system infectious diseases
Infectious diseases of the central nervous system (CNS) can be divided into bacterial, tuberculous, viral, fungal, parasitic infections, etc. Early etiological treatment is often the most crucial means to reduce the mortality rate of patients with central nervous system infections, reduce complications and sequelae, and improve prognosis. The initial clinical ...read more
Trends and perspectives in the rational management of CNS disorders
Central nervous system (CNS) diseases enforce a significant global health burden, driving ongoing efforts to improve our understanding and effectiveness of therapy. This issue investigates current advances in the discipline, focusing on the understanding as well as therapeutic handling of various CNS diseases. The issue covers a variety of diseases, ...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
Related Articles
-
Imaging of Organ Metabolism in Obesity and Diabetes: Treatment Perspectives
Current Pharmaceutical Design Erythropoietin and Oxidative Stress
Current Neurovascular Research Predictors of Left Ventricular Ejection Fraction Improvement after Radiofrequency Catheter Ablation in Patients with PVC-Induced Cardiomyopathy: A Systematic Review
Current Cardiology Reviews Mesenchymal Stromal Cell Therapy for Cardio Renal Disorders
Current Pharmaceutical Design The Vectorcardiogram and the Main Dromotropic Disturbances
Current Cardiology Reviews Hemodynamic Assessment and In vivo Catabolism of Adenosine 5’-triphosphate in Doxorubicin or Isoproterenol-induced Cardiovascular Toxicity
Drug Metabolism Letters S-nitrosation/Denitrosation in Cardiovascular Pathologies: Facts and Concepts for the Rational Design of S-nitrosothiols
Current Pharmaceutical Design Nitric Oxide-Derived Oxidants with a Focus on Peroxynitrite: Molecular Targets,Cellular Responses and Therapeutic Implications
Current Pharmaceutical Design The Impact of Methodology and Confounding Variables on the Association Between Major Depression and Coronary Heart Disease: Review and Recommendations
Current Psychiatry Reviews Treatment of Fabry Disease: Current and Emerging Strategies
Current Pharmaceutical Biotechnology Side Effects of Clozapine and Some Other Psychoactive Drugs
Current Drug Safety The Cardiac Microvasculature in Hypertension, Cardiac Hypertrophy and Diastolic Heart Failure
Current Vascular Pharmacology Reactive Oxygen Species and Antioxidants in the Pathophysiology of Cardiovascular Disease: Does the Actual Knowledge Justify a Clinical Approach?
Current Vascular Pharmacology Editorial: Look for Changes in 2016
Current Molecular Medicine Diabetes and Chronic Heart Failure: From Diabetic Cardiomyopathy to Therapeutic Approach
Endocrine, Metabolic & Immune Disorders - Drug Targets Endothelial Cell Regulation of Cardiac Metabolism Following Diabetes
Cardiovascular & Hematological Disorders-Drug Targets Antioxidants in the Practice of Medicine; What Should the Clinician Know?
Cardiovascular & Hematological Disorders-Drug Targets Written Consent to Use the Drug in Children: The Problem of Off-Label Drugs
Current Pharmaceutical Design Cardioprotection by Targeting the Pool of Resident and Extracardiac Progenitors
Current Drug Targets Diabetes and Complications: Cellular Signaling Pathways, Current Understanding and Targeted Therapies
Current Drug Targets