Abstract
The unfolded protein response (UPR) plays a vital role in maintaining cell homeostasis as a consequence of endoplasmic reticulum (ER) stress. However, prolonged UPR activity leads to cell death. This time-dependent dual functionality of the UPR represents the adaptive and cytotoxic pathways that result from ER stress. Chronic UPR activation in systemic and neurodegenerative diseases has been identified as an early sign of cellular dyshomeostasis.
The Protein Kinase R-like ER Kinase (PERK) pathway is one of three major branches in the UPR, and it is the only one to modulate protein synthesis as an adaptive response. The specific identification of prolonged PERK activity has been correlated with the progression of disorders such as diabetes, Alzheimer’s disease, and cancer, suggesting that PERK plays a role in the pathology of these disorders. For the first time, the term “PERK-opathies” is used to group these diseases in which PERK mediates detriment to the cell culminating in chronic disorders. This article reviews the literature documenting links between systemic disorders with the UPR, but with a specific emphasis on the PERK pathway. Then, articles reporting links between the UPR, and more specifically PERK, and neurodegenerative disorders are presented. Finally, a therapeutic perspective is discussed, where PERK interventions could be potential remedies for cellular dysfunction in chronic neurodegenerative disorders.
Keywords: eIF2α, EIF2AK3, endoplasmic reticulum, neurodegeneration, PERK, tau, unfolded protein response.
Current Alzheimer Research
Title:PERK-opathies: An Endoplasmic Reticulum Stress Mechanism Underlying Neurodegeneration
Volume: 13 Issue: 2
Author(s): Michelle C. Bell, Shelby E. Meier, Alexandria L. Ingram and Jose F. Abisambra
Affiliation:
Keywords: eIF2α, EIF2AK3, endoplasmic reticulum, neurodegeneration, PERK, tau, unfolded protein response.
Abstract: The unfolded protein response (UPR) plays a vital role in maintaining cell homeostasis as a consequence of endoplasmic reticulum (ER) stress. However, prolonged UPR activity leads to cell death. This time-dependent dual functionality of the UPR represents the adaptive and cytotoxic pathways that result from ER stress. Chronic UPR activation in systemic and neurodegenerative diseases has been identified as an early sign of cellular dyshomeostasis.
The Protein Kinase R-like ER Kinase (PERK) pathway is one of three major branches in the UPR, and it is the only one to modulate protein synthesis as an adaptive response. The specific identification of prolonged PERK activity has been correlated with the progression of disorders such as diabetes, Alzheimer’s disease, and cancer, suggesting that PERK plays a role in the pathology of these disorders. For the first time, the term “PERK-opathies” is used to group these diseases in which PERK mediates detriment to the cell culminating in chronic disorders. This article reviews the literature documenting links between systemic disorders with the UPR, but with a specific emphasis on the PERK pathway. Then, articles reporting links between the UPR, and more specifically PERK, and neurodegenerative disorders are presented. Finally, a therapeutic perspective is discussed, where PERK interventions could be potential remedies for cellular dysfunction in chronic neurodegenerative disorders.
Export Options
About this article
Cite this article as:
Bell C. Michelle, Meier E. Shelby, Ingram L. Alexandria and Abisambra F. Jose, PERK-opathies: An Endoplasmic Reticulum Stress Mechanism Underlying Neurodegeneration, Current Alzheimer Research 2016; 13 (2) . https://dx.doi.org/10.2174/1567205013666151218145431
DOI https://dx.doi.org/10.2174/1567205013666151218145431 |
Print ISSN 1567-2050 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-5828 |
Call for Papers in Thematic Issues
New Advances in the Prevention, Diagnosis, Treatment, and Rehabilitation of Alzheimer's Disease
Aims and Scope: Introduction: Alzheimer's disease (AD) poses a significant global health challenge, with an increasing prevalence that demands concerted efforts to advance our understanding and strategies for prevention, diagnosis, treatment, and rehabilitation. This thematic issue aims to bring together cutting-edge research and innovative approaches from multidisciplinary perspectives to address ...read more
Current updates on the Role of Neuroinflammation in Neurodegenerative Disorders
Neuroinflammation is an invariable hallmark of chronic and acute neurodegenerative disorders and has long been considered a potential drug target for Alzheimer?s disease (AD) and dementia. Significant evidence of inflammatory processes as a feature of AD is provided by the presence of inflammatory markers in plasma, CSF and postmortem brain ...read more
Deep Learning for Advancing Alzheimer's Disease Research
Alzheimer's disease (AD) poses a significant global health challenge, with an increasing number of individuals affected yearly. Deep learning, a subfield of artificial intelligence, has shown immense potential in various domains, including healthcare. This thematic issue of Current Alzheimer Research explores the application of deep learning techniques in advancing our ...read more
Diagnostic and therapeutic biomarkers of dementia
Dementia affects 18 million people worldwide. Dementia is a syndrome of symptoms caused by brain disease, usually chronic or progressive, clinically characterized by multiple impairments of higher cortical functions such as memory, thinking, orientation, and learning. In addition, in the course of dementia, cognitive deficits are observed, which often hinder ...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
- Announcements
Related Articles
-
Discovery and Development of Topoisomerase Inhibitors as Anticancer Agents
Mini-Reviews in Medicinal Chemistry Developments of Polo-like Kinase 1 (Plk1) Inhibitors as Anti-Cancer Agents
Mini-Reviews in Medicinal Chemistry Radiopharmaceuticals for Oncology Drug Development: A Pharmaceutical Industry Perspective
Current Pharmaceutical Design Nanoparticle Albumin - Bound (NAB) Technology is a Promising Method for Anti-Cancer Drug Delivery
Recent Patents on Anti-Cancer Drug Discovery Aptamers as Targeting Delivery Devices or Anti-cancer Drugs for Fighting Tumors
Current Drug Metabolism T Cell Tuning for Tumour Therapy: Enhancing Effector Function and Memory Potential of Therapeutic T cells
Current Gene Therapy CARD Proteins as Therapeutic Targets in Cancer
Current Drug Targets Transposable Elements in Cancer and Other Human Diseases
Current Cancer Drug Targets Anti-Neoplastic Activity of 1,3-Diaza-2-Functionalized-Adamantan-6-One Compounds Against Melanoma Cells
Medicinal Chemistry Mechanisms of Tumor Cell Necrosis
Current Pharmaceutical Design Design of New Oxazaphosphorine Anticancer Drugs
Current Pharmaceutical Design The Role of the Tyrosine Kinase Inhibitor STI571 in the Treatment of Cancer
Current Cancer Drug Targets The Efficacy and Mechanism of Proteasome Inhibitors in Solid Tumor Treatment
Recent Patents on Anti-Cancer Drug Discovery The Genetic Landscapes of Inflammation-Driven Gastrointestinal Tract Cancers
Current Pharmaceutical Design Biomarkers for Systemic Therapy in Ovarian Cancer
Current Cancer Drug Targets Molecular Mechanisms of Tumor Invasion and Metastasis: An Integrated View
Current Molecular Medicine Is Fibroblast Growth Factor Receptor 4 a Suitable Target of Cancer Therapy?
Current Pharmaceutical Design Editorial (Thematic Issue: Revisiting the Revolution: Examining the Evolving Role of Antiangiogenic Therapy in Cancer)
Current Drug Targets The Development of MetAP-2 Inhibitors in Cancer Treatment
Current Medicinal Chemistry Recent Developments in Nanoparticle Based Targeted Delivery of Chemotherapeutics
Current Bioactive Compounds