Format

Send to:

Choose Destination
See comment in PubMed Commons below
FEBS Lett. 2006 Apr 3;580(8):2081-6. Epub 2006 Mar 10.

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

Author information

  • 1Institut de Physiologie et Biologie Cellulaires, CNRS UMR 6187, Universit√© de Poitiers, 40 avenue du recteur Pineau, Poitiers 86022, France. cnorez@ext.univ-poitiers.fr

Abstract

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) prescribed for the treatment of Gaucher disease, our findings provide the basis for future clinical evaluation of miglustat in CF patients.

PMID:
16546175
[PubMed - indexed for MEDLINE]
Free full text
PubMed Commons home

PubMed Commons

0 comments
How to join PubMed Commons

    Supplemental Content

    Full text links

    Icon for Wiley
    Loading ...
    Write to the Help Desk