Cystic fibrosis transmembrane conductance regulator intracellular processing, trafficking, and opportunities for mutation-specific treatment.

Hdl Handle:
http://hdl.handle.net/10147/207954
Title:
Cystic fibrosis transmembrane conductance regulator intracellular processing, trafficking, and opportunities for mutation-specific treatment.
Authors:
Rogan, Mark P; Stoltz, David A; Hornick, Douglas B
Affiliation:
Department of Respiratory Medicine, Waterford Regional Hospital, Waterford,, Ireland.
Citation:
Chest. 2011 Jun;139(6):1480-90.
Journal:
Chest
Issue Date:
1-Feb-2012
URI:
http://hdl.handle.net/10147/207954
DOI:
10.1378/chest.10-2077
PubMed ID:
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?
Language:
eng
MeSH:
Cystic Fibrosis/*etiology/metabolism/*therapy; Cystic Fibrosis Transmembrane Conductance Regulator/*physiology; Humans; Mutation/physiology; Protein Transport/physiology; Signal Transduction/physiology
ISSN:
1931-3543 (Electronic); 0012-3692 (Linking)

Full metadata record

DC FieldValue Language
dc.contributor.authorRogan, Mark Pen_GB
dc.contributor.authorStoltz, David Aen_GB
dc.contributor.authorHornick, Douglas Ben_GB
dc.date.accessioned2012-02-01T10:52:27Z-
dc.date.available2012-02-01T10:52:27Z-
dc.date.issued2012-02-01T10:52:27Z-
dc.identifier.citationChest. 2011 Jun;139(6):1480-90.en_GB
dc.identifier.issn1931-3543 (Electronic)en_GB
dc.identifier.issn0012-3692 (Linking)en_GB
dc.identifier.pmid21652558en_GB
dc.identifier.doi10.1378/chest.10-2077en_GB
dc.identifier.urihttp://hdl.handle.net/10147/207954-
dc.description.abstractRecent 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?en_GB
dc.language.isoengen_GB
dc.subject.meshCystic Fibrosis/*etiology/metabolism/*therapyen_GB
dc.subject.meshCystic Fibrosis Transmembrane Conductance Regulator/*physiologyen_GB
dc.subject.meshHumansen_GB
dc.subject.meshMutation/physiologyen_GB
dc.subject.meshProtein Transport/physiologyen_GB
dc.subject.meshSignal Transduction/physiologyen_GB
dc.titleCystic fibrosis transmembrane conductance regulator intracellular processing, trafficking, and opportunities for mutation-specific treatment.en_GB
dc.contributor.departmentDepartment of Respiratory Medicine, Waterford Regional Hospital, Waterford,, Ireland.en_GB
dc.identifier.journalChesten_GB
dc.description.provinceMunster-

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