Journal article
Cystic fibrosis transmembrane conductance regulator intracellular processing, trafficking, and opportunities for mutation-specific treatment
Chest, Vol.139(6), pp.1480-1490
06/2011
DOI: 10.1378/chest.10-2077
PMID: 21652558
Abstract
Recent advances in basic science have greatly expanded our understanding of the cystic fibrosis (CF) transmembrane conductance regulator (CFTR), the chloride and bicarbonate channel that is encoded by the gene, which is mutated in patients with CF. We review the structure, function, biosynthetic processing, and intracellular trafficking of CFTR and discuss the five classes of mutations and their impact on the CF phenotype. The therapeutic discussion is focused on the significant progress toward CFTR mutation-specific therapies. We review the results of encouraging clinical trials examining orally administered therapeutics, including agents that promote read-through of class I mutations (premature termination codons); correctors, which overcome the CFTR misfolding that characterizes the common class II mutation F508del; and potentiators, which enhance the function of class III or IV mutated CFTR at the plasma membrane. Long-term outcomes from successful mutation-specific treatments could finally answer the question that has been lingering since and even before the CFTR gene discovery: Will therapies that specifically restore CFTR-mediated chloride secretion slow or arrest the deleterious cascade of events leading to chronic infection, bronchiectasis, and end-stage lung disease?
Details
- Title: Subtitle
- Cystic fibrosis transmembrane conductance regulator intracellular processing, trafficking, and opportunities for mutation-specific treatment
- Creators
- Mark P Rogan - Department of Respiratory Medicine, Waterford Regional Hospital, Waterford, IrelandDavid A Stoltz - Department of Internal Medicine, Division of Pulmonary, Critical Care, and Occupational Medicine, University of Iowa Roy J. and Lucille A. Carver College of Medicine, Iowa City, IADouglas B Hornick - Department of Internal Medicine, Division of Pulmonary, Critical Care, and Occupational Medicine, University of Iowa Roy J. and Lucille A. Carver College of Medicine, Iowa City, IA. Electronic address: douglas-hornick@uiowa.edu
- Resource Type
- Journal article
- Publication Details
- Chest, Vol.139(6), pp.1480-1490
- Publisher
- United States
- DOI
- 10.1378/chest.10-2077
- PMID
- 21652558
- ISSN
- 0012-3692
- eISSN
- 1931-3543
- Language
- English
- Date published
- 06/2011
- Academic Unit
- Roy J. Carver Department of Biomedical Engineering; Molecular Physiology and Biophysics; Pulmonary, Critical Care, and Occupational Medicine; Internal Medicine
- Record Identifier
- 9984025565302771
Metrics
28 Record Views