Misfolded G Protein-Coupled Receptors and Endocrine Disease. Molecular Mechanisms and Therapeutic Prospects
Abstract
:1. Introduction
2. Loss-of-Function Diseases Caused by Folding Defects in GPCRs Associated Endocrine Function
2.1. Misfolded GnRHRs and Hypogonadotropic Hypogonadism
2.2. Misfolded Gonadotropin Receptors as a Cause of Hypergonadotropic Hypergonadism
3. Strategies to Rescue Misfolded GPCRs Leading to Endocrine Disorders
3.1. General Approaches to Rescue Function of Misfolded Proteins
3.2. Chemical Approaches
3.3. Pharmacological Approaches
4. Conclusions
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
References
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Disease | GPCR | Pharmacoperone |
---|---|---|
Nephrogenic diabetes insípidus | V2R | Satavaptan, relcovaptan, VPA985, YM087, tolvaptan, OPC31260 [20,48,49,50] |
Isolated hypogonadotropic hypogonadism | GnRHR | IN3, IN30, Q89, A177775, TAK-013 (reviewed in Ref. [22]) |
Familial hypocalciuric hypercalcemia | CaR | NPS R-568 (reviewed in Ref. [36]) |
Male pseudohermaphroditism and hypergonadotropic hypogonadism | LHR | Org 42,599 [51,52] |
Primary ovarian failure | FSHR | Org41841, CAN1404 [53,54] |
Congenital hypothyroidism | TSHR | - |
Familial glucocorticoid resistance | MC2R (ACTHR) | - |
Obesity | MCR3, MCR4 | ML00253764, Ipsen 5i, THIQ [9,13,38,39,55] |
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Ulloa-Aguirre, A.; Zariñán, T.; Jardón-Valadez, E. Misfolded G Protein-Coupled Receptors and Endocrine Disease. Molecular Mechanisms and Therapeutic Prospects. Int. J. Mol. Sci. 2021, 22, 12329. https://doi.org/10.3390/ijms222212329
Ulloa-Aguirre A, Zariñán T, Jardón-Valadez E. Misfolded G Protein-Coupled Receptors and Endocrine Disease. Molecular Mechanisms and Therapeutic Prospects. International Journal of Molecular Sciences. 2021; 22(22):12329. https://doi.org/10.3390/ijms222212329
Chicago/Turabian StyleUlloa-Aguirre, Alfredo, Teresa Zariñán, and Eduardo Jardón-Valadez. 2021. "Misfolded G Protein-Coupled Receptors and Endocrine Disease. Molecular Mechanisms and Therapeutic Prospects" International Journal of Molecular Sciences 22, no. 22: 12329. https://doi.org/10.3390/ijms222212329