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• W4309354338 endingPage "134" @default.
• W4309354338 startingPage "65" @default.
• W4309354338 abstract "Adequate protein folding and trafficking represent crucial processes in the proper functioning of cells. Their integrity is ensured by highly regulated multistep quality control mechanisms at different locations in the protein synthesis and secretory pathway. For membrane proteins such as G protein-coupled receptors (GPCR), folding and quality control occur mainly in the endoplasmic reticulum and the Golgi complex. Mutations in the coding sequence of GPCR often lead to incomplete or inappropriate folding that results in their recognition and their intracellular retention by the quality control system, preventing their targeting to the plasma membrane, where they usually mediate their action. Given the pleiotropic roles of GPCR in recognizing many signaling molecules (e.g. hormones, neurotransmitters, cytokines, and odors), such mutations often lead to pathologies known as conformational diseases. Among them, the best characterized were retinitis pigmentosa, nephrogenic diabetes insipidus, hypogonadotropic hypogonadism, and severe early-onset obesity resulting from mutation in the genes coding for rhodopsin (RHO), vasopressin type-2 receptor (V2R), gonadotropin-releasing hormone receptor (GnRHR), and melanocortin type-4 receptor (MC4R), respectively. In recent years, molecules known as chemical and pharmacological chaperones were found to promote the proper folding, trafficking, and function of mutant forms of GPCR responsible for conformational diseases, thus opening avenues for the development of new treatments for these ailments. Here, we briefly review the mechanisms involved in protein folding and its quality control, and focus on the mechanism of action of GPCR-targeting pharmacological chaperones, their in vivo action, as well as their potentials and challenges for clinical development." @default.
• W4309354338 created "2022-11-26" @default.
• W4309354338 creator A5053833598 @default.
• W4309354338 creator A5065778043 @default.
• W4309354338 creator A5079411745 @default.
• W4309354338 date "2022-11-14" @default.
• W4309354338 modified "2023-10-01" @default.
• W4309354338 title "Pharmacological Chaperones" @default.
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