Gastroenterology
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The most common form of the disease-causing cystic fibrosis transmembrane conductance regulator mutation, DeltaF508, leads to a misfolded protein that undergoes endoplasmic reticulum-associated degradation. Retrieval of misfolded protein from the cis-Golgi or pre-Golgi intermediate compartment is a critical factor in endoplasmic reticulum retention and degradation of DeltaF508 protein. Therefore, the inhibition of retrograde Golgi-to-endoplasmic reticulum traffic by the alkalinization of Golgi lumen may permit functional DeltaF508 protein to reach the cell surface. ⋯ We found that base treatments correct misfolded cystic fibrosis transmembrane conductance regulator-induced defects in vitro and in vivo. These results imply that the alkalization of intracellular compartments, in particular, Golgi or pre-Golgi intermediate compartments, can be a potential therapeutic target for the loss-of-function type of conformational diseases.
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Comment Letter
Stool DNA: a viable option for colorectal cancer screening.