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
Novel Treatments in Subarachnoid Hemorrhage
The current landscape of therapeutic strategies for subarachnoid hemorrhage (SAH), a significant adverse neurological event commonly resulting from the rupture of intracranial aneurysms, is rapidly evolving. Through an in-depth exploration of the natural history of SAH, historical treatment approaches, and emerging management modalities, the present work aims to provide a ...read more
Pathogenic Proteins in Neurodegenerative Diseases: From Mechanisms to Treatment Modalities
The primary objective of this thematic issue is to elucidate the molecular mechanisms by which pathogenic proteins contribute to neurodegenerative diseases and to highlight current and emerging therapeutic strategies aimed at mitigating their effects. By bringing together cutting-edge research and reviews, this issue aims to: 1.Enhance Understanding: Provide a comprehensive ...read more
Role of glial cells in autism spectrum disorder: Molecular mechanism and therapeutic approaches
Emerging evidence suggests that glial cells may play a pivotal role in neuroanatomical and behavioral changes found in autism spectrum disorder (ASD). Many individuals with ASD experience a neuro-immune system abnormalities throughout life, which implicates a potential role of microglia in the pathogenesis of ASD. Dysfunctional astrocytes and oligodendrocytes were ...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
-
Parvovirus B19 (B19V) Infection and Pregnancy
Current Pediatric Reviews Iodinated Contrast Media in Diagnostic Imaging: Cardiovascular Side Effects
Current Pharmacogenomics and Personalized Medicine The Role of the Methoxyphenol Apocynin, a Vascular NADPH Oxidase Inhibitor, as a Chemopreventative Agent in the Potential Treatment of Cardiovascular Diseases
Current Vascular Pharmacology Mechanisms of Intimal Hyperplasia Learned from a Murine Carotid Artery Ligation Model
Current Vascular Pharmacology Emerging Molecular Targets for Treatment of Erectile Dysfunction: Vascular and Regenerative Therapies on the Horizon
Current Drug Targets Role of AMPK in Diabetic Cardiovascular Complications: An Overview
Cardiovascular & Hematological Disorders-Drug Targets Emerging Role for Antioxidant Therapy in Protection Against Diabetic Cardiac Complications: Experimental and Clinical Evidence for Utilization of Classic and New Antioxidants
Current Cardiology Reviews Making the Most of Pathological Specimens: Molecular Diagnosis in Formalin-Fixed, Paraffin Embedded Tissue
Current Drug Targets New Targeted Therapies for Thyroid Cancer
Current Genomics A Glance on the Role of Bacterial Siderophore from the Perspectives of Medical and Biotechnological Approaches
Current Drug Targets Unconventional Players on the Striated Muscle Field: microRNAs, Signaling Pathways and Epigenetic Regulators
Current Stem Cell Research & Therapy The Tree of Sirtuins and the Garden of Cardiovascular Youth
Current Vascular Pharmacology New Developments in Anthracycline-Induced Cardiotoxicity
Current Medicinal Chemistry mTOR in Growth and Protection of Hypertrophying Myocardium
Cardiovascular & Hematological Agents in Medicinal Chemistry Bone Marrow Stem Cell Therapy for Myocardial Angiogenesis
Current Vascular Pharmacology Combinations Against Combinations: Associations of Anti-HIV 1 Reverse Transcriptase Drugs Challenged by Constellations of Drug Resistance Mutations
Current Drug Metabolism Diabetes Mellitus: Channeling Care through Cellular Discovery
Current Neurovascular Research Cardiolipin Metabolism and the Role it Plays in Heart Failure and Mitochondrial Supercomplex Formation
Cardiovascular & Hematological Disorders-Drug Targets Signs and Related Mechanisms of Ethanol Hepatotoxicity
Current Drug Abuse Reviews Role of Drug Metabolism in the Cytotoxicity and Clinical Efficacy of Anthracyclines
Current Drug Metabolism