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
-
Bioconjugation of Polymers: A Novel Platform for Targeted Drug Delivery
Current Pharmaceutical Design Adrenomedullin and Nitric Oxide: Implications for the Etiology and Treatment of Primary Brain Tumors
CNS & Neurological Disorders - Drug Targets Thrombocytopenia in HIV Disease: Clinical Relevance, Physiopathology and Management
Current Medicinal Chemistry - Cardiovascular & Hematological Agents Antitumoral Potential of Snake Venom Phospholipases A2 and Synthetic Peptides
Current Pharmaceutical Biotechnology Repositioning of DHFR Inhibitors
Current Topics in Medicinal Chemistry Prevalence of Dilated Cardiomyopathy in HIV-Infected African Patients Not Receiving HAART: A Multicenter, Observational, Prospective, Cohort Study in Rwanda
Current HIV Research Oncolytic Viruses for Induction of Anti-Tumor Immunity
Current Pharmaceutical Biotechnology Recent Trends in Targeted Anticancer Prodrug and Conjugate Design
Current Medicinal Chemistry Paclitaxel Formulations: Challenges and Novel Delivery Options
Current Drug Delivery Poly(ADP-Ribose) Polymerase Inhibitors: New Pharmacological Functions and Potential Clinical Implications
Current Pharmaceutical Design Trafficking of HIV-1 RNA: Recent Progress Involving Host Cell RNABinding Proteins
Current Genomics The Implication of Platelet Activating Factor in Cancer Growth and Metastasis: Potent Beneficial Role of PAF-Inhibitors and Antioxidants
Infectious Disorders - Drug Targets Dual-Specificity MAP Kinase Phosphatases as Targets of Cancer Treatment
Anti-Cancer Agents in Medicinal Chemistry Approaches for Administering Chemotherapy in the Intensive Care Unit
Current Drug Safety Secondary Neoplasms in Children Treated for Cancer
Current Pediatric Reviews Antioxidant Therapy for the Treatment of Oxidative Stress Associated to Cancer and Cancer- Related Anorexia/Cachexia
Current Nutrition & Food Science Recent Developments of Platinum-based Anticancer Drugs- Detection and Analysis in Biological Samples
Current Organic Chemistry Apoptosis in Anthracycline Cardiomyopathy
Current Pediatric Reviews Signaling Pathways Responsible for Cancer Cell Invasion as Targets for Cancer Therapy
Current Cancer Drug Targets Animal Models of Systemic Sclerosis
Current Pharmaceutical Design