Rescue of functional delF508-CFTR channels in cystic fibrosis epithelial cells by the α-glucosidase inhibitor miglustat

In the disease cystic fibrosis (CF), the most common mutation delF508 results in endoplasmic reticulum retention of misfolded CF gene proteins (CFTR). We show that the α-1,2-glucosidase inhibitor miglustat ( N-butyldeoxynojirimycin, NB-DNJ) prevents delF508-CFTR/calnexin interaction and restores cAM...

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Published inFEBS letters Vol. 580; no. 8; pp. 2081 - 2086
Main Authors Norez, Caroline, Noel, Sabrina, Wilke, Martina, Bijvelds, Marcel, Jorna, Huub, Melin, Patricia, DeJonge, Hugo, Becq, Frederic
Format Journal Article
LanguageEnglish
Published England Elsevier B.V 03.04.2006
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Summary:In the disease cystic fibrosis (CF), the most common mutation delF508 results in endoplasmic reticulum retention of misfolded CF gene proteins (CFTR). We show that the α-1,2-glucosidase inhibitor miglustat ( N-butyldeoxynojirimycin, NB-DNJ) prevents delF508-CFTR/calnexin interaction and restores cAMP-activated chloride current in epithelial CF cells. Moreover, miglustat rescues a mature and functional delF508-CFTR in the intestinal crypts of ileal mucosa from delF508 mice. Since miglustat is an orally active orphan drug (Zavesca ®) prescribed for the treatment of Gaucher disease, our findings provide the basis for future clinical evaluation of miglustat in CF patients.
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ISSN:0014-5793
1873-3468
DOI:10.1016/j.febslet.2006.03.010