Pharmacological chaperones: Novel therapeutic strategies to rescue defective protein folding and trafficking

Numerous inherited diseases are found to result from gene mutations that lead to Mutant proteins, which can not fold correctly, fall to undergo trafficking, and are unable to reach their sites of action. Recently, pharmacological chaperones are developed as new therapeutics to rescue proteins defective in folding and trafficking. They are small cell-permeable chemicals, such as substrates, receptor ligands and enzyme inhibitors, which selectively recognize mutant proteins in the endoplasmic reticulum, correct their folding, stabilize the conformation, facilitate their trafficking to destination and yield functional proteins directly. Pharmacological chaperones represent promising avenues for the treatment of endocrine and metabolic diseases. They rescue a number of mutant proteins destined for the plasma membrane or organelles, such as ABC transporters, G-protein-coupled receptors, lysosomal enzymes and so on. Currently, one pharmacological chaperone has been Successfully tested in clinical studies, and a lot of pharmacological chaperones have been tested and displayed positive results in cellular system and animal. This indicates that pharmacological chaperones will have great potential and broad prospects for clinical application in the future.