Pharmacological chaperones: a new twist on receptor folding.

Protein misfolding is at the root of several genetic human diseases. These diseases do not stem from mutations within the active domain of the proteins, but from mutations that disrupt their three-dimensional conformation, which leads to their intracellular retention by the quality control apparatus of the cell. Facilitating the escape of the mutant proteins from the quality control system by lowering the temperature of the cells or by adding chemicals that assist folding (chemical chaperones) can result in proteins that are fully functional despite their mutation. The discovery that ligands with pharmacological selectivity (pharmacological chaperones) can rescue the proper targeting and function of misfolded proteins, including receptors, might help to develop new treatments for 'conformational diseases'.