Abstract
Alzheimer’s disease (AD) is a progressive neurodegenerative disorder that is characterized by progressive loss of memory and cognitive impairment. Aggregation of amyloid-β (Aβ) peptides is the crucial factor in the onset of AD. The toxic Aβ peptides Aβ40 and Aβ42 are produced from the Aβ precursor protein (APP), a transmembrane protein which is folded and modified in endoplasmic reticulum (ER). ER is the main organelle for the synthesis and processing of nearly all proteins as well as the main cellular source of Ca2+. Under stress conditions, three main ER pathways including inositol- requiring enzyme 1, protein kinase RNA-like ER kinase, and activating transcription factor 6 become activated causing the accumulation of unfolded or misfolded proteins within ER lumen. These pathways manage the stress by regulating the expression of chaperones and enzymes involved in protein folding. Several studies have reported the dysfunction of these stress-sensing pathways in pathological conditions, including neurodegenerative diseases. Recent studies have proposed that neuronal death in AD arises from dysfunction of the ER. Here, we will review recent research findings on the interaction between ER and mitochondria, and its effect on apoptotic pathways. We further provide insights into studies which suggest the role of ER in animal and/or cellular models of AD. Therapeutic strategies that modulate ER could represent a promising approach for prevention or treatment of AD.
Current Drug Targets
Title:Molecular Mechanism Aspect of ER Stress in Alzheimer's Disease: Current Approaches and Future Strategies
Volume: 14 Issue: 1
Author(s): Niloufar Ansari and Fariba Khodagholi
Affiliation:
Abstract: Alzheimer’s disease (AD) is a progressive neurodegenerative disorder that is characterized by progressive loss of memory and cognitive impairment. Aggregation of amyloid-β (Aβ) peptides is the crucial factor in the onset of AD. The toxic Aβ peptides Aβ40 and Aβ42 are produced from the Aβ precursor protein (APP), a transmembrane protein which is folded and modified in endoplasmic reticulum (ER). ER is the main organelle for the synthesis and processing of nearly all proteins as well as the main cellular source of Ca2+. Under stress conditions, three main ER pathways including inositol- requiring enzyme 1, protein kinase RNA-like ER kinase, and activating transcription factor 6 become activated causing the accumulation of unfolded or misfolded proteins within ER lumen. These pathways manage the stress by regulating the expression of chaperones and enzymes involved in protein folding. Several studies have reported the dysfunction of these stress-sensing pathways in pathological conditions, including neurodegenerative diseases. Recent studies have proposed that neuronal death in AD arises from dysfunction of the ER. Here, we will review recent research findings on the interaction between ER and mitochondria, and its effect on apoptotic pathways. We further provide insights into studies which suggest the role of ER in animal and/or cellular models of AD. Therapeutic strategies that modulate ER could represent a promising approach for prevention or treatment of AD.
Export Options
About this article
Cite this article as:
Ansari Niloufar and Khodagholi Fariba, Molecular Mechanism Aspect of ER Stress in Alzheimer's Disease: Current Approaches and Future Strategies, Current Drug Targets 2013; 14 (1) . https://dx.doi.org/10.2174/1389450111314010012
DOI https://dx.doi.org/10.2174/1389450111314010012 |
Print ISSN 1389-4501 |
Publisher Name Bentham Science Publisher |
Online ISSN 1873-5592 |
Call for Papers in Thematic Issues
New drug therapy for eye diseases
Eyesight is one of the most critical senses, accounting for over 80% of our perceptions. Our quality of life might be significantly affected by eye disease, including glaucoma, diabetic retinopathy, dry eye, etc. Although the development of microinvasive ocular surgery reduces surgical complications and improves overall outcomes, medication therapy is ...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
-
Hitting the Golden TORget: Curcumin’s Effects on mTOR Signaling
Anti-Cancer Agents in Medicinal Chemistry Hypoxia-Inducible Factors and Sphingosine 1-Phosphate Signaling
Anti-Cancer Agents in Medicinal Chemistry Targeting Mitochondria in Fighting Cancer
Current Pharmaceutical Design Astatine Radiopharmaceuticals: Prospects and Problems
Current Radiopharmaceuticals Elastin-Like Recombinamers As Smart Drug Delivery Systems
Current Drug Targets Insights into the Role of Matrix Metalloproteinases and Tissue Inhibitor of Metalloproteinases in Health and Disease
Current Chemical Biology Natural Molecules as Talented Inhibitors of Nucleotide Pyrophosphatases/ Phosphodiesterases (PDEs)
Current Topics in Medicinal Chemistry Signal Pathways Mediating Antidepressant and Antipsychotic Drugs on Neuronal Cell Survival
Current Medicinal Chemistry - Central Nervous System Agents Glioblastoma Multiforme and its Cell Interruption
Current Cancer Therapy Reviews Post-Wortmannin Era: Novel Phosphoinositide 3-Kinase Inhibitors with Potential Therapeutic Applications
Current Enzyme Inhibition Measles Virus as An Oncolytic Vector Platform
Current Gene Therapy Nucleic Acid Aptamers Against Protein Kinases
Current Medicinal Chemistry Co-targeting EGFR and Autophagy Impairs Ovarian Cancer Cell Survival during Detachment from the ECM
Current Cancer Drug Targets Drugs Interfering with Apoptosis in Breast Cancer
Current Pharmaceutical Design Development of Focal Adhesion Kinase Inhibitors in Cancer Therapy
Anti-Cancer Agents in Medicinal Chemistry Diagnostic and Therapeutic Applications of Exosome Nanovesicles in Lung Cancer: State-of-The-Art
Anti-Cancer Agents in Medicinal Chemistry Protein Kinases as Drug Targets in Human and Animal Diseases
Current Enzyme Inhibition Patent Selections
Recent Patents on CNS Drug Discovery (Discontinued) Advances in Synergistic Combinations of Chinese Herbal Medicine for the Treatment of Cancer
Current Cancer Drug Targets Tyrosine Kinase Inhibitors – A Review on Pharmacology, Metabolism and Side Effects
Current Drug Metabolism