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
Techniques of Drug Repurposing: Delivering a new life to Herbs & Drugs
Of late, with the adaptation of innovative approaches and integration of advancements made towards medical sciences as well as the availability of a wide range of tools; several therapeutic challenges are being translated into viable clinical solutions, with a high degree of efficacy, safety, and selectivity. With a better understanding ...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
-
Bcl-2 Family Proteins Regulate Apoptosis and Epithelial to Mesenchymal Transition by Calcium Signals
Current Pharmaceutical Design Sex-Gender Differences in Diabetes Vascular Complications and Treatment
Endocrine, Metabolic & Immune Disorders - Drug Targets The Role of local Insulin-like Growth Factor-1 Isoforms in the Pathophysiology of Skeletal Muscle
Current Genomics Oxidative Stress During Myocardial Ischaemia and Heart Failure
Current Pharmaceutical Design p38 Mitogen-Activated Protein Kinase: A Critical Node Linking Insulin Resistance and Cardiovascular Diseases in Type 2 Diabetes Mellitus
Endocrine, Metabolic & Immune Disorders - Drug Targets Target Peptide Recognition by S100P Protein and Role of Central Linker Region and Dimer Interface
Protein & Peptide Letters HIV-1 Infection In Children: A Clinical and Immunologic Overview
Current HIV Research Testosterone and Cardioprotection Against Myocardial Ischemia
Cardiovascular & Hematological Disorders-Drug Targets Induced Pluripotent Stem Cells as a Model for Therapy Personalization of Pediatric Patients: Disease Modeling and Drug Adverse Effects Prevention
Current Medicinal Chemistry Urine Cells-derived iPSCs: An Upcoming Frontier in Regenerative Medicine
Current Medicinal Chemistry Immunoadsorption Therapy for Patients with Dilated Cardiomyopathy and Heart Failure
Current Cardiology Reviews Lipotoxicity Disrupts Erythrocyte Function: A Perspective
Cardiovascular & Hematological Disorders-Drug Targets A Review on Novel Ligand Targeted Delivery for Cardiovascular Disorder
Current Drug Delivery Bicycloheptylamine-Doxorubicin Conjugate: Synthesis and Anticancer Activities in σ2 Receptor-Expressing Cell Lines
Medicinal Chemistry Inherited Muscle Diseases Towards Improvements of the Mouse Model Catalogue
Current Genomics Connexin43 and Myocardial Ischemia-Reperfusion Injury
Cardiovascular & Hematological Disorders-Drug Targets New Cell Therapy Using Bone Marrow-Derived Stem Cells/Endothelial Progenitor Cells to Accelerate Neovascularization in Healing of Experimental Ulcerative Colitis
Current Pharmaceutical Design Patent Selections
Recent Patents on Medical Imaging Prevalence of Major Cardiac Events of Anthracycline-Induced Cardiotoxicity in Southwestern Iran: Different Response Patterns to Cumulative Dose
Current Drug Therapy Helminth Infections and Cardiovascular Diseases: Toxocara Species is Contributing to the Disease
Current Cardiology Reviews