Abstract
Cystic Fibrosis (CF) is largely caused by protein misfolding and the loss of function of a plasma membrane anion channel known as the cystic fibrosis transmembrane conductance regulator (CFTR). The most common CF-causing mutation, F508del, leads to severe conformational defect in CFTR. The cellular chaperone machinery plays an important role in CFTR biogenesis and quality control. Multiple attempts have been made to improve the cell surface functional expression of the mutant CFTR by modulating the expression of components of the cellular chaperone machinery. The efficacy of such an approach has been low largely due to the severe intrinsic folding defects of the F508del CFTR. Moreover, the impact of chaperone perturbation on the chaperone machinery itself and on other physiologically important proteins might lead to potentially severe side effects. Approaches aimed at disrupting chaperone-CFTR interactions show greater efficacy, and are compatible with small-molecule drug discovery and gene therapy. Combination between chaperone modulators and F508del correctors might further enhance potency and specificity. As molecular chaperones play important roles in regulating inflammation and immunity, they can be potential targets for controlling airway infection and inflammation in patients. If such effects can be synergized with chaperone-mediated regulation of CFTR biogenesis and quality control, more efficacious therapeutics will be developed to combat CF lung disease.
Keywords: CFTR, cystic fibrosis, drug discovery, F508del, immunity, inflammation, molecular chaperone, protein folding.
Graphical Abstract
Current Drug Targets
Title:Targeting Molecular Chaperones for the Treatment of Cystic Fibrosis: Is It a Viable Approach?
Volume: 16 Issue: 9
Author(s): Ashley Heard, Jake Thompson, Jessica Carver, Michelle Bakey and X. Robert Wang
Affiliation:
Keywords: CFTR, cystic fibrosis, drug discovery, F508del, immunity, inflammation, molecular chaperone, protein folding.
Abstract: Cystic Fibrosis (CF) is largely caused by protein misfolding and the loss of function of a plasma membrane anion channel known as the cystic fibrosis transmembrane conductance regulator (CFTR). The most common CF-causing mutation, F508del, leads to severe conformational defect in CFTR. The cellular chaperone machinery plays an important role in CFTR biogenesis and quality control. Multiple attempts have been made to improve the cell surface functional expression of the mutant CFTR by modulating the expression of components of the cellular chaperone machinery. The efficacy of such an approach has been low largely due to the severe intrinsic folding defects of the F508del CFTR. Moreover, the impact of chaperone perturbation on the chaperone machinery itself and on other physiologically important proteins might lead to potentially severe side effects. Approaches aimed at disrupting chaperone-CFTR interactions show greater efficacy, and are compatible with small-molecule drug discovery and gene therapy. Combination between chaperone modulators and F508del correctors might further enhance potency and specificity. As molecular chaperones play important roles in regulating inflammation and immunity, they can be potential targets for controlling airway infection and inflammation in patients. If such effects can be synergized with chaperone-mediated regulation of CFTR biogenesis and quality control, more efficacious therapeutics will be developed to combat CF lung disease.
Export Options
About this article
Cite this article as:
Heard Ashley, Thompson Jake, Carver Jessica, Bakey Michelle and Wang Robert X., Targeting Molecular Chaperones for the Treatment of Cystic Fibrosis: Is It a Viable Approach?, Current Drug Targets 2015; 16 (9) . https://dx.doi.org/10.2174/1389450116666150518102831
DOI https://dx.doi.org/10.2174/1389450116666150518102831 |
Print ISSN 1389-4501 |
Publisher Name Bentham Science Publisher |
Online ISSN 1873-5592 |
Related Books

- Author Guidelines
- Bentham Author Support Services (BASS)
- 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
Related Articles
-
The Heme-Heme Oxygenase System in Wound Healing; Implications for Scar Formation
Current Drug Targets Herbal Nanoformulations for Asthma Treatment
Current Pharmaceutical Design Electrical Impedance Scanning - A New Diagnostic Tool in Cancer Detection: Current Status and Recent Developments
Current Medical Imaging Targeted Drug Delivery Systems and Their Therapeutic Applications in Cancer and Immune Pathological Conditions
Infectious Disorders - Drug Targets Antibody-Based Therapies in Systemic Lupus Erythematosus
Mini-Reviews in Medicinal Chemistry Systems Medicine Approaches to Improving Understanding, Treatment, and Clinical Management of Neuroendocrine Prostate Cancer
Current Pharmaceutical Design Structural Magnetic Resonance Imaging Findings in Posttraumatic Stress Disorder and Their Response to Treatment: A Systematic Review
Current Psychiatry Reviews Central Nervous System Abnormalities in Fibromyalgia and Chronic Fatigue Syndrome: New Concepts in Treatment
Current Pharmaceutical Design A Proteome-Level Computational Biology Insight on Sequence Based Aggregation Propensity Profile of Human Hydrolase Structural Enzymes
Current Biotechnology Undressing the Fungal Cell Wall/Cell Membrane - the Antifungal Drug Targets
Current Pharmaceutical Design Monoclonal Antibodies and their Target Specificity Against SARS-CoV-2 Infections: Perspectives and Challenges
Recent Patents on Biotechnology Extracellular Vesicles as Novel Delivery Tools for Cancer Treatment
Current Cancer Drug Targets Flame Retardants in Indoor Dust - A Review on the Levels of Polybrominated Diphenyl Ethers and Hexabromocyclododecanes
Current Organic Chemistry The Heme Oxygenase/Biliverdin Reductase Pathway in Drug Research and Development
Current Drug Metabolism Coumarin and Derivates as Lipid Lowering Agents
Current Topics in Medicinal Chemistry Epidemiology and Prevention of Bacterial Infections in Patients with Hematologic Malignancies
Infectious Disorders - Drug Targets The Treatment of Cardiovascular Disease Continuum: Focus on Pharmacologic Management and RAS Blockade
Current Clinical Pharmacology Anticipation in Lynch Syndrome: Where We Are Where We Go
Current Genomics Review on Patents for Ubiquitin-Proteasome Inhibitor as Medical Advance in Major Human Diseases
Recent Patents on Biomedical Engineering (Discontinued) Characterization and antiherpetic activity of native and chemically sulfated polysaccharide from <i>Adenanthera pavonina</i>
Current Pharmaceutical Biotechnology