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
-
Autosomal Recessive Hereditary Spastic Paraplegia: A Rare Case of a Family with Phenotypic Variation
Current Pharmacogenomics and Personalized Medicine Hyperhomocysteinemia in Movement Disorders: Current Evidence and Hypotheses
Current Vascular Pharmacology The Quest for Novel Biomarkers in Early Diagnosis of Diabetic Neuropathy
Current Proteomics Common Themes in RNA Subcellular Transport, Stress Granule Formation and Abnormal Protein Aggregation
Current Chemical Biology Heme Oxygenase -1 Gene Therapy: Recent Advances and Therapeutic Applications
Current Gene Therapy The Therapeutic Potential of Melatonin in Neurological Disorders
Recent Patents on Endocrine, Metabolic & Immune Drug Discovery A Common Biological Mechanism in Cancer and Alzheimers Disease?
Current Alzheimer Research L-Dopa Prodrugs: An Overview of Trends for Improving Parkinsons Disease Treatment
Current Pharmaceutical Design Exploring Multiple Sclerosis (MS) and Amyotrophic Lateral Scler osis (ALS) as Neurodegenerative Diseases and their Treatments: A Review Study
Current Topics in Medicinal Chemistry Current Options in the Treatment of Mitochondrial Diseases
Recent Patents on CNS Drug Discovery (Discontinued) Proteomics as Applied to Inherited Metabolic Diseases
Current Proteomics Skeletal Muscle in Motor Neuron Diseases: Therapeutic Target and Delivery Route for Potential Treatments
Current Drug Targets The Cannabinoids Switch of Oxidative Stress: A Double-Edged Sword
Mini-Reviews in Organic Chemistry Astroglial Connexins in Neurological and Neuropsychological Disorders and Radiation Exposure
Current Medicinal Chemistry Recent Updates of N-Type Calcium Channel Blockers with Therapeutic Potential for Neuropathic Pain and Stroke
Current Topics in Medicinal Chemistry Microglia-Neuron Interaction in Inflammatory and Degenerative Diseases: Role of Cholinergic and Noradrenergic Systems
CNS & Neurological Disorders - Drug Targets Cannabinoids: Occurrence and Medicinal Chemistry
Current Medicinal Chemistry Vitamins and Cognition: A Nutrigenomics Perspective
Current Nutrition & Food Science Oxidative Stress Targeting Amyloid Beta Accumulation and Clearance in Alzheimer’s Disease: Insight into Pathological Mechanisms and Therapeutic Strategies
Current Psychopharmacology The Unbiased Search of Biomarkers in Neurodegenerative Diseases
Current Pharmaceutical Biotechnology