Abstract
Heat shock proteins are members of a large family that function normally in nascent protein folding and the removal of damaged proteins and are able to respond to cellular stresses such as thermal insult to prevent catastrophic protein aggregation. A number of the most common neurodegenerative disorders such as Alzheimer’s and Parkinson’s diseases are characterized by such abnormal protein folding and aggregation, and the induction of the heat shock response is observed in these cases through their increased expression and often localization within the inclusions. Tau proteins form the major structural component of the neurofibrillary protein aggregates that correlate with cognitive decline in Alzheimer’s disease, and appropriately this abnormal tau is targeted for corrective action by the heat shock proteins that recognize sequence motifs that are normally masked though microtubule binding. This specific heat shock response to the formation of abnormal tau can also be targeted pharmacologically to inhibit the refolding pathways and drive the degradation of tau species that are thought to be pathogenic. This review discusses the recent advances of the roles of heat shock proteins in this process.
Keywords: Heat shock proteins, neurodegeneration, aggregation, chaperones, proteasome, ubiquitin, autophagy, tau protein.
Current Alzheimer Research
Title:Targeting Heat Shock Proteins in Tauopathies
Volume: 7 Issue: 8
Author(s): M. DeTure, C. Hicks and L. Petrucelli
Affiliation:
Keywords: Heat shock proteins, neurodegeneration, aggregation, chaperones, proteasome, ubiquitin, autophagy, tau protein.
Abstract: Heat shock proteins are members of a large family that function normally in nascent protein folding and the removal of damaged proteins and are able to respond to cellular stresses such as thermal insult to prevent catastrophic protein aggregation. A number of the most common neurodegenerative disorders such as Alzheimer’s and Parkinson’s diseases are characterized by such abnormal protein folding and aggregation, and the induction of the heat shock response is observed in these cases through their increased expression and often localization within the inclusions. Tau proteins form the major structural component of the neurofibrillary protein aggregates that correlate with cognitive decline in Alzheimer’s disease, and appropriately this abnormal tau is targeted for corrective action by the heat shock proteins that recognize sequence motifs that are normally masked though microtubule binding. This specific heat shock response to the formation of abnormal tau can also be targeted pharmacologically to inhibit the refolding pathways and drive the degradation of tau species that are thought to be pathogenic. This review discusses the recent advances of the roles of heat shock proteins in this process.
Export Options
About this article
Cite this article as:
DeTure M., Hicks C. and Petrucelli L., Targeting Heat Shock Proteins in Tauopathies, Current Alzheimer Research 2010; 7 (8) . https://dx.doi.org/10.2174/156720510793611565
DOI https://dx.doi.org/10.2174/156720510793611565 |
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
-
The Involvement of Post-Translational Modifications in Alzheimer's Disease
Current Alzheimer Research Cucurbitacin E, An Experimental Lead Triterpenoid with Anticancer, Immunomodulatory and Novel Effects Against Degenerative Diseases. A Mini-Review
Current Topics in Medicinal Chemistry Review: Alternative Splicing (AS) of Genes As An Approach for Generating Protein Complexity
Current Genomics Two Nitrogen-containing Ligands as Inhibitors of Metal-Induced Amyloid β-Peptide Aggregation
CNS & Neurological Disorders - Drug Targets Role and Treatment of Mitochondrial DNA-Related Mitochondrial Dysfunction in Sporadic Neurodegenerative Diseases
Current Pharmaceutical Design Regression of Oxidative Stress by Targeting eNOS and Nrf2/ARE Signaling: A Guided Drug Target for Cardiovascular Diseases
Current Topics in Medicinal Chemistry Mitochondrial Dysfunctions in Bipolar Disorder: Effect of the Disease and Pharmacotherapy
CNS & Neurological Disorders - Drug Targets Towards Retinoid Therapy for Alzheimers Disease
Current Alzheimer Research New Insights into Biological Markers of Frontotemporal Lobar Degeneration Spectrum
Current Medicinal Chemistry From Nature to Market: Examples of Natural Products that Became Drugs
Recent Patents on Biotechnology The Ubiquitin Proteasome System as a Potential Target for the Treatment of Neurodegenerative Diseases
Current Pharmaceutical Design Platelet-Derived Secreted Amyloid-Precursor Protein-β as a Marker for Diagnosing Alzheimer’s Disease
Current Neurovascular Research Development of Neurotrophic Molecules for Treatment of Neurode-generation
Current Protein & Peptide Science Astrocytes and Inflammasome: A Possible Crosstalk in Neurological Diseases
Current Medicinal Chemistry Impairment of Store-operated Calcium Entry: Implications in Alzheimer’s Neurodegeneration
Current Alzheimer Research Statins: Are They All the Same?
Current Drug Therapy Employing New Cellular Therapeutic Targets for Alzheimers Disease: A Change for the Better?
Current Neurovascular Research Microglial Senescence
CNS & Neurological Disorders - Drug Targets Investigational Selective Melatoninergic Ligands for Receptor Subtype MT2
Mini-Reviews in Medicinal Chemistry Warming Up to New Possibilities with the Capsaicin Receptor TRPV1: mTOR, AMPK, and Erythropoietin
Current Neurovascular Research