Researchers from the University of North Carolina at Chapel Hill have identified a key molecular mechanism that may account for the development of cystic fibrosis, which about 1 in 3000 children are born with in the US every year.
The findings, published February 29 in the open-access journal PLoS Computational Biology, add new knowledge to understanding the development of this disease and may also point the way to new corrective treatments.
Cystic fibrosis (CF) is a fatal disease caused by a defective gene that produces a misshapen form of the cystic fibrosis transmembrane conductance regulator (CFTR) protein. People with cystic fibrosis do not have enough CFTR for their cells to work normally because their bodies quickly destroy the mutant protein. The deletion of this protein specifically occurs in a major domain of CFTR called NBD1. Earlier experimental studies have shown that the mutant NBD1 has an increased tendency to misfold, resulting in the premature degradation of CFTR.
In CF, the molecular basis of this increased misfolding tendency has remained elusive, said team leader Nikolay Dokholyan.
“Understanding molecular etiology of the disease is a key step to developing pharmaceutical strategies to fight this disease,” Dokholyan said.