Rescue of F508del CFTR: Commentary on “F508del CFTR with two altered RXR motifs escapes from ER quality control but its channel activity is thermally sensitive” [Biochim. Biohys. Acta Biomembranes …]
نویسندگان
چکیده
منابع مشابه
Tezacaftor/Ivacaftor in Subjects with Cystic Fibrosis and F508del/F508del-CFTR or F508del/G551D-CFTR.
RATIONALE Tezacaftor (formerly VX-661) is an investigational small molecule that improves processing and trafficking of the cystic fibrosis transmembrane conductance regulator (CFTR) in vitro, and improves CFTR function alone and in combination with ivacaftor. OBJECTIVES To evaluate the safety and efficacy of tezacaftor monotherapy and of tezacaftor/ivacaftor combination therapy in subjects w...
متن کاملFunctional Rescue of F508del-CFTR Using Small Molecule Correctors
High-throughput screens for small molecules that are effective in "correcting" the functional expression of F508del-CFTR have yielded several promising hits. Two such compounds are currently in clinical trial. Despite this success, it is clear that further advances will be required in order to restore 50% or greater of wild-type CFTR function to the airways of patients harboring the F508del-CFT...
متن کاملA chemical corrector modifies the channel function of F508del-CFTR.
The deletion of Phe-508 (F508del) constitutes the most prevalent cystic fibrosis-causing mutation. This mutation leads to cystic fibrosis transmembrane conductance regulator (CFTR) misfolding and retention in the endoplasmic reticulum and altered channel activity in mammalian cells. This folding defect can however be partially overcome by growing cells expressing this mutant protein at low (27 ...
متن کاملRescue of Murine F508del CFTR Activity in Native Intestine by Low Temperature and Proteasome Inhibitors
Most patients with Cystic Fibrosis (CF) carry at least one allele with the F508del mutation, resulting in a CFTR chloride channel protein with a processing, gating and stability defect, but with substantial residual activity when correctly sorted to the apical membranes of epithelial cells. New therapies are therefore aimed at improving the folding and trafficking of F508del CFTR, (CFTR correct...
متن کاملCalpain Inhibition Promotes the Rescue of F508del-CFTR in PBMC from Cystic Fibrosis Patients
A basal calpain activity promotes the limited proteolysis of wild type (WT) cystic fibrosis conductance regulator (CFTR), inducing the internalization of the split channel. This process contributes to the regulation in the level of the active CFTR at the plasma membranes. In peripheral blood mononuclear cells (PBMC) from 16 healthy donors, the inhibition of calpain activity induces a 3-fold inc...
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ژورنال
عنوان ژورنال: Biochimica et Biophysica Acta (BBA) - Biomembranes
سال: 2006
ISSN: 0005-2736
DOI: 10.1016/j.bbamem.2006.03.033