CONDUCTANCE OF IMPROPERLY FOLDED PROTEINS THROUGH THE SECRETORY PATHWAY

摘要

This invention provides the methodology and agents for treating disease or clinical condition which is at least partly the result of endoplasmic reticulum-associated retention of proteins. Thus, the methods and agents of the present invention provide for the release of normally retained proteins from the endoplasmic reticulum. The present invention is particularly useful for treating any disease or clinical condition which is at least partly the result of endoplasmic reticulum-associated retention or degradation of mis-assembled or mis-folded proteins. In particular, thapsigargin, cyclopiazonic acid, DBHQ or halothane can be used to allow the release of DELTA F508CFTR or of a secretion-incompetent variant null (Hong Kong) of alpha 1-antitrypsin, in order to treat cystic fibrosis or chronic obstructive pulmonary disease (pulmonary emphysema) respectively.