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
-
AMPK and its Activator Berberine in the Treatment of Neurodegenerative Diseases
Current Pharmaceutical Design Protein Aggregation in Alzheimers Disease and Other Neoropathological Disorders
Current Alzheimer Research Can Environmentally Relevant Levels of Aluminium Promote the Onset and Progression of Neurodegenerative Diseases?
Current Inorganic Chemistry (Discontinued) Evidence for the Role of Luteinizing Hormone in Alzheimer Disease
Endocrine, Metabolic & Immune Disorders - Drug Targets Axonal Ionic Pathophysiology in Human Peripheral Neuropathy and Motor Neuron Disease
Current Neurovascular Research Growth Hormone and Insulin-Like Growth Factor-I as an Endocrine Axis in Alzheimers Disease
Endocrine, Metabolic & Immune Disorders - Drug Targets Selenium and Clinical Trials: New Therapeutic Evidence for Multiple Diseases
Current Medicinal Chemistry Recent Patents in CNS Drug Discovery: The Management of Inflammation in the Central Nervous System
Recent Patents on CNS Drug Discovery (Discontinued) Neuron-Microglia Interactions in Motor Neuron Degeneration. The Inflammatory Hypothesis in Amyotrophic Lateral Sclerosis Revisited
Current Medicinal Chemistry FoxO3a Governs Early Microglial Proliferation and Employs Mitochondrial Depolarization with Caspase 3, 8, and 9 Cleavage During Oxidant Induced Apoptosis
Current Neurovascular Research Quinazolines as Apoptosis Inducers and Inhibitors: A Review of Patent Literature
Recent Patents on Anti-Cancer Drug Discovery Nutraceuticals for Promoting Longevity
Current Nutraceuticals Preparation of Hymenialdisine, Analogues and Their Evaluation as Kinase Inhibitors
Current Medicinal Chemistry Brain-Derived Neurotrophic Factor: A Dynamic Gatekeeper of Neural Plasticity
Current Molecular Pharmacology Neurodegeneration with Dementia: From Fundamentals of Pathology to Clinical Imaging by MRI and SPECT.
Current Medical Imaging Histone Deacetylase Inhibitors In Inflammatory Disease
Current Topics in Medicinal Chemistry Aptamers: Selection, Modification and Application to Nervous System Diseases
Current Medicinal Chemistry Drosophila Models of Proteinopathies: the Little Fly that Could
Current Pharmaceutical Design Effects of Thyroid Hormones and their Metabolites on Learning and Memory in Normal and Pathological Conditions
Current Drug Metabolism Intrinsically Disordered Domains, Amyloids and Protein Liquid Phases: Evolving Concepts and Open Questions
Protein & Peptide Letters