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A pharmacological chaperone (or pharmacoperone, from "protein chaperone") is a small molecule that enters cells and serves as a molecular scaffolding in order to cause otherwise-misfolded mutant proteins to fold and route correctly within the cell.
Mutation of proteins often causes molecular misfolding, which results in protein misrouting within the cell. Accordingly, mutant molecules may retain proper function but end up in parts of the cell where the function is inappropriate, or even deleterious, to cell function. Misfolded proteins are usually recognized by the quality-control system of the cell and retained (and often destroyed or recycled)in the endoplasmic reticulum.
Pharmacoperones correct the folding of misfolded proteins, allowing them to pass through the cell's quality-control system and become correctly routed. Since mutations often cause disease by causing misfolding and misrouting, pharmacoperones are potentially therapeutic agents, since they are able to correct this defect.
- Migalastat is a pharmacological chaperone for the treatment of Fabry disease.
- In 2013, mice with a disease that makes the males unable to father offspring were cured by use of pharmacoperones.
- "Drugs to fix "misfolded" proteins could cure a range of diseases". Gizmag.com. Retrieved 2013-12-10.
- Janovick, J. A.; Stewart, M. D.; Jacob, D.; Martin, L. D.; Deng, J. M.; Stewart, C. A.; Wang, Y.; Cornea, A.; Chavali, L.; Lopez, S.; Mitalipov, S.; Kang, E.; Lee, H. -S.; Manna, P. R.; Stocco, D. M.; Behringer, R. R.; Conn, P. M. (2013). "Restoration of testis function in hypogonadotropic hypogonadal mice harboring a misfolded GnRHR mutant by pharmacoperone drug therapy". Proceedings of the National Academy of Sciences. doi:10.1073/pnas.1315194110.
- Conn, P.M. and Janovick, J.A., A New Understanding of Protein Mutation Unfolds, American Scientist 93:314-321, 2005.