Journal
FEBS LETTERS
Volume 580, Issue 8, Pages 2081-2086Publisher
ELSEVIER SCIENCE BV
DOI: 10.1016/j.febslet.2006.03.010
Keywords
cystic fibrosis transmembrane conductance regulator; miglustat; castanospermine; calnexin; chloride channels; delF508-mice
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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 alpha-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 (R)) prescribed for the treatment of Gaucher disease, our findings provide the basis for future clinical evaluation of miglustat in CF patients. (c) 2006 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.
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