Pharmacological chaperone action on G-protein-coupled receptors.
An increasing number of genetic diseases are found to result from mutations that lead to retention of the affected proteins in the endoplasmic reticulum, where they are recognized as misfolded by the quality control system. Several of these conformational diseases involve mutations in G-protein-coupled receptors. Recent studies demonstrated that pharmacologically selective compounds, termed pharmacological chaperones, can stabilize the misfolded receptors, facilitating their export from the endoplasmic reticulum to the plasma membrane, where they can be active. Such functional rescue suggests that pharmacological chaperones could represent novel therapeutic agents for the treatment of conformational diseases. Although only a few examples are currently available, the observation that pharmacological chaperones can also favour the folding of wild-type G-protein-coupled receptors indicates that these compounds could have wide applications.
Bernier
Virginie
V
Département de Biochimie and Groupe de Recherche sur le Système Nerveux Autonome, Université de Montréal, Montréal, Québec, Canada H3C 3J7.
Bichet
Daniel G
DG
Bouvier
Michel
M
D000818:Animals; D004700:Endocrine System Diseases / Q000378:metabolism; D004721:Endoplasmic Reticulum / Q000378:metabolism; D006801:Humans; D008659:Metabolic Diseases / Q000378:metabolism; D009154:Mutation; D011487:Protein Conformation; D017510:Protein Folding; D021381:Protein Transport; D043562:Receptors, G-Protein-Coupled / Q000235:genetics / Q000378:metabolism*
D043562:Receptors, G-Protein-Coupled