2006-04-03
Rescue of functional delF508-CFTR channels in cystic fibrosis epithelial cells by the α-glucosidase inhibitor miglustat
Publication
Publication
F E B S Letters , Volume 580 - Issue 8 p. 2081- 2086
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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doi.org/10.1016/j.febslet.2006.03.010, hdl.handle.net/1765/68917 | |
F E B S Letters | |
Organisation | Department of Biochemistry |
Norez, C., Noel, S., Wilke, M., Bijvelds, M., Jorna, H., Melin, P., … Becq, F. (2006). Rescue of functional delF508-CFTR channels in cystic fibrosis epithelial cells by the α-glucosidase inhibitor miglustat. F E B S Letters, 580(8), 2081–2086. doi:10.1016/j.febslet.2006.03.010 |