Cystic fibrosis is caused by mutations in the gene encoding the cystic fibrosis transmembrane
conductance regulator (CFTR). The most common mutation, DeltaF508, results in the
production of a misfolded CFTR protein that is retained in the endoplasmic reticulum
and targeted for degradation. Curcumin is a nontoxic Ca-adenosine triphosphatase pump
inhibitor that can be administered to humans safely. Oral administration of curcumin
to homozygous DeltaF508 CFTR mice in doses comparable, on a weight-per-weight basis,
to those well tolerated by humans corrected these animals' characteristic nasal potential
difference defect. These effects were not observed in mice homozygous for a complete
knockout of the CFTR gene. Curcumin also induced the functional appearance of DeltaF508
CFTR protein in the plasma membranes of transfected baby hamster kidney cells. Thus,
curcumin treatment may be able to correct defects associated with the homozygous expression
of DeltaF508 CFTR.
