Article
Biochemistry & Molecular Biology
Naoki Harada, Yumi Arahori, Mai Okuyama, Paula B. Luis, Akil Joseph, Tomoya Kitakaze, Naoki Goshima, Claus Schneider, Hiroshi Inui, Ryoichi Yamaji
Summary: This study identifies the activation of G protein-coupled receptor 97 (GPR97) by curcumin and investigates its molecular mechanisms.
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
(2022)
Article
Endocrinology & Metabolism
Jung Soo Lim, Samuel W. Plaska, Juilee Rege, William E. Rainey, Adina F. Turcu
Summary: Somatic gene mutations that promote inappropriate intracellular calcium entrance have been found in most aldosterone-producing adenomas (APAs). Angiotensin II and ACTH have been shown to increase aldosterone production from APAs, but responses to hormonal stimuli may vary based on different aldosterone-driver mutations. Transcript expression of AGTR1, MC2R, and MRAP differed in APAs with different mutations, suggesting that ATPase-mutated APAs may be more responsive to ACTH than KCNJ5-mutated APAs.
FRONTIERS IN ENDOCRINOLOGY
(2021)
Article
Biochemistry & Molecular Biology
Ren-Lei Ji, Ya-Xiong Tao
Summary: Two new human MRAP2 splice variants were identified in this study, and the effects of MRAP1 and MRAP2 on MC3R and MC4R were investigated. The results suggest that MRAPs play important roles in the signaling and regulation of neural MC3R and MC4R.
Article
Endocrinology & Metabolism
Yuta Tezuka, Kae Ishii, Lili Zhao, Yuto Yamazaki, Ryo Morimoto, Hironobu Sasano, Aaron M. Udager, Fumitoshi Satoh, Adina F. Turcu
Summary: Dynamic HPA testing revealed significant differences in plasma steroid levels between patients with APA and BPA, with APA patients showing higher concentrations of specific steroids both at baseline and in response to ACTH stimulation. The discriminatory power of steroid measurements taken 15 minutes post-ACTH stimulation was particularly high, suggesting it could potentially replace adrenal vein sampling in some PA patients.
JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM
(2021)
Review
Cell Biology
Haoran Jiang, Daniella Galtes, Jialu Wang, Howard A. Rockman
Summary: This review explores the signaling pathways, dynamic structures, and physiological relevance of the three most important GPCR signaling effectors in the cardiovascular system: heterotrimeric G proteins, GPCR kinases (GRKs), and 8-arrestins. It summarizes their prominent roles in GPCR pharmacology before transitioning into less well-explored areas. The application of new technologies has contributed to an increasing understanding of GPCR structure and downstream effectors.
AMERICAN JOURNAL OF PHYSIOLOGY-CELL PHYSIOLOGY
(2022)
Article
Pharmacology & Pharmacy
Estefania Moreno, Nil Casajuana-Martin, Michael Coyle, Baruc Campos Campos, Ewa Galaj, Claudia Llinas del Torrent, Arta Seyedian, William Rea, Ning-Sheng Cai, Alessandro Bonifazi, Benjamin Floran, Zheng-Xiong Xi, Xavier Guitart, Vicent Casado, Amy H. Newman, Christopher Bishop, Leonardo Pardo, Sergi Ferre
Summary: This study provides evidence that heteromerization of G protein-coupled receptors (GPCRs), specifically dopamine D1 and D3 receptors, can influence the pharmacological properties of selective ligands. In vivo experiments support the involvement of D1R-D3R heteromers in the development of L-DOPA-induced dyskinesia in Parkinson's disease, suggesting the potential of targeting GPCR heteromers for drug development.
PHARMACOLOGICAL RESEARCH
(2022)
Article
Biochemistry & Molecular Biology
Juergen Einsiedel, Maximilian F. Schmidt, Harald Huebner, Peter Gmeiner
Summary: A broadly applicable synthesis method was developed for peptides incorporating mixed disulfides between cysteine and homocysteine and cysteamine. The method was successfully applied to pharmacologically relevant GPCR ligands and showed covalent binding to neurotensin receptor 1 in a radioligand depletion study.
BIOORGANIC & MEDICINAL CHEMISTRY
(2022)
Review
Pharmacology & Pharmacy
Bui San Thai, Ling Yeong Chia, Anh T. N. Nguyen, Chengxue Qin, Rebecca H. Ritchie, Dana S. Hutchinson, Andrew Kompa, Paul J. White, Lauren T. May
Summary: Heart failure remains a significant cause of morbidity and mortality worldwide. Current treatment options have limitations, leading to many patients progressing to advanced stages. Exploration of novel therapeutics targeting G protein-coupled receptors (GPCRs) has shown promise, but efficacy and unwanted effects remain as challenges.
BRITISH JOURNAL OF PHARMACOLOGY
(2023)
Article
Biochemistry & Molecular Biology
Ren-Lei Ji, Shan-Shan Jiang, Ya-Xiong Tao
Summary: The neural melanocortin receptors (MCRs) and their accessory proteins MRAP1 and MRAP2 play crucial roles in regulating energy homeostasis. This study reveals that MRAP1 and MRAP2s have species-specific effects on canine neural MCRs, providing a better understanding of their regulation.
Review
Pharmacology & Pharmacy
Mydirah Littlepage-Saunders, Michael J. Hochstein, Doris S. Chang, Kari A. Johnson
Summary: Dopamine transmission in the striatum is regulated by various G protein-coupled receptors (GPCRs) that bind neuromodulators, including dopamine itself. These GPCRs can modulate dopamine release by acting on different components of the dopaminergic circuitry and can have distinct effects on behavior and psychoactive drug actions. This review discusses the mechanisms by which GPCRs regulate dopaminergic transmission and their relevance to the effects of psychoactive drugs on physiology and behavior.
BRITISH JOURNAL OF PHARMACOLOGY
(2023)
Article
Biochemistry & Molecular Biology
Damian Jacenik, Pawel Hikisz, Ellen J. Beswick, Jakub Fichna
Summary: Among the various adhesion G protein-coupled receptors, ADGRF5 stands out with its unique domains in the N-terminal tail that play a critical role in cell-cell and cell-matrix interactions, as well as cell adhesion. Although the biology of ADGRF5 is still not fully understood, accumulating evidence suggests its fundamental importance in both health and disease. Recent studies have highlighted its potential diagnostic value in osteoporosis and cancers, and ongoing research indicates its relevance to other diseases as well. This article provides a comprehensive overview of the current understanding of ADGRF5 in human disease physiology and pathophysiology, emphasizing its potential as a novel therapeutic target in various areas.
BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR BASIS OF DISEASE
(2023)
Review
Biochemistry & Molecular Biology
Raudah Lazim, Donghyuk Suh, Jai Woo Lee, Thi Ngoc Lan Vu, Sanghee Yoon, Sun Choi
Summary: The presence of GPCR dimers has sparked research into their importance in disease pathogenesis and drug design, uncovering new signaling pathways and potential therapeutic targets. The increasing influence of computational methods in research is providing new avenues for understanding the functions and interactions of GPCRs.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Review
Pharmacology & Pharmacy
Alastair C. Keen, Manuela Jorg, Michelle L. L. Halls
Summary: The ubiquitin-proteasome system is a major pathway for protein degradation in cells, and methods have been developed to exploit this system for targeted protein degradation. Targeted protein degraders have been useful tools in discovery research and are being developed as therapeutics. However, most targeted protein degrader technologies have been developed for cytosolic proteins, while examples for G protein-coupled receptor (GPCR) degradation are limited. This review discusses the strategies used for applying targeted protein degradation to GPCRs and explores alternative approaches used for degrading other integral membrane proteins.
BRITISH JOURNAL OF PHARMACOLOGY
(2023)
Review
Pharmacology & Pharmacy
Rina Pokhrel, Alexandra L. Morgan, Harley R. Robinson, Martin J. Stone, Simon R. Foster
Summary: G protein-coupled receptor (GPCR) activation triggers complex intracellular signalling networks, which have important implications for receptor biology and drug discovery. Phosphoproteomics has emerged as a powerful tool for investigating these networks and accelerating the discovery of new therapeutic targets.
BRITISH JOURNAL OF PHARMACOLOGY
(2023)
Article
Biochemistry & Molecular Biology
Shuai Luo, Peng Zhang, Wei Miao, Jie Xiong
Summary: This study provides the first comprehensive genome-wide identification of GPCRs in ciliates, identifying 492 GPCRs in 24 ciliates. GPCRs in ciliates can be assigned to four families, with most belonging to family A. Gene duplication events play a role in the expansion of the GPCR superfamily in ciliates. This study improves our understanding of the evolution and function of GPCRs in ciliates.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Endocrinology & Metabolism
T. V. Novoselova, L. F. Chan, A. J. L. Clark
BEST PRACTICE & RESEARCH CLINICAL ENDOCRINOLOGY & METABOLISM
(2018)
Article
Biochemistry & Molecular Biology
Tatiana V. Novoselova, Mashal Hussain, Peter J. King, Leonardo Guasti, Louise A. Metherell, Marika Charalambous, Adrian J. L. Clark, Li F. Chan
Review
Biochemistry & Molecular Biology
Avinaash Maharaj, Ashwini Maudhoo, Li F. Chan, Tatiana Novoselova, Rathi Prasad, Louise A. Metherell, Leonardo Guasti
JOURNAL OF STEROID BIOCHEMISTRY AND MOLECULAR BIOLOGY
(2019)
Review
Endocrinology & Metabolism
Tatiana Novoselova, Peter King, Leonardo Guasti, Louise A. Metherell, Adrian J. L. Clark, Li F. Chan
ENDOCRINE CONNECTIONS
(2019)
Article
Biochemistry & Molecular Biology
A. Maharaj, J. Williams, T. Bradshaw, T. Guran, D. Braslavsky, J. Casas, L. F. Chan, L. A. Metherell, R. Prasad
JOURNAL OF STEROID BIOCHEMISTRY AND MOLECULAR BIOLOGY
(2020)
Article
Multidisciplinary Sciences
Hadar Israeli, Oksana Degtjarik, Fabrizio Fierro, Vidicha Chunilal, Amandeep Kaur Gill, Nicolas J. Roth, Joaquin Botta, Vadivel Prabahar, Yoav Peleg, Li F. Chan, Danny Ben-Zvi, Peter J. McCormick, Masha Y. Niv, Moran Shalev-Benami
Summary: This study elucidated the mechanism of MC4R activation, identified a molecular switch for initiating satiation signaling, and suggested the involvement of calcium in agonist efficacy. These findings may guide the design of future weight-management drugs.
Article
Health Care Sciences & Services
R. Asaad Baksh, Andre Strydom, Sarah E. Pape, Li F. Chan, Martin C. Gulliford
Summary: This study found that individuals with Down syndrome are more susceptible to being diagnosed with COVID-19, especially those with chronic respiratory diseases. Therefore, they are particularly vulnerable during viral pandemics and should be prioritized for vaccinations.
JOURNAL OF GENERAL INTERNAL MEDICINE
(2022)
Article
Pediatrics
Christopher M. Parry, Li F. Chan, Daniel F. Carr, Daniel B. Hawcutt
Summary: PDGFD is expressed in the human adrenal cell line, H295R, and its expression can be influenced by beclometasone and steroidogenesis agonists/antagonists. This study provides in vitro evidence supporting a potential link between the PDGF and cortisol production pathways, indicating that PDGFD variants may impact an individual's sensitivity to corticosteroid-induced adrenal suppression.
PEDIATRIC RESEARCH
(2023)
Article
Multidisciplinary Sciences
Cristina Perez-Ternero, Aisah A. Aubdool, Raj Makwana, Gareth J. Sanger, Roland H. Stimson, Li F. Chan, Amie J. Moyes, Adrian J. Hobbs
Summary: C-type natriuretic peptide (CNP) plays a crucial role in lipid homeostasis and energy balance by regulating the expression of uncoupling protein-1 and lipid utilization. CNP exerts these metabolic regulatory actions by inhibiting sympathetic thermogenic programming and reducing peroxisome proliferator-activated receptor-gamma coactivator-1 alpha expression, while driving adipogenesis via NPR-B/protein kinase-G.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2022)
Article
Endocrinology & Metabolism
Aisha A. Aslam, R. Asaad Baksh, Sarah E. Pape, Andre Strydom, Martin C. Gulliford, Li F. Chan
Summary: Individuals with Down syndrome have a higher incidence of diabetes, especially at a younger age. Obesity is associated with an increased risk of type 2 diabetes in individuals with Down syndrome.
Article
Endocrinology & Metabolism
Rachel Forfar, Mashal Hussain, Puneet Khurana, Jennifer Cook, Steve Lewis, Dillon Popat, David Jackson, Ed McIver, Jeff Jerman, Debra Taylor, Adrian J. L. Clark, Li F. Chan
Summary: The overproduction of ACTH leads to significant morbidity, but there is currently no effective medical treatment to directly block its action. This study identified a highly specific MC2R antagonist, providing a foundation for the clinical investigation of small-molecule ACTH antagonists as therapeutic agents.
ENDOCRINE CONNECTIONS
(2022)
Article
Endocrinology & Metabolism
Valeria Hasenmajer, Rosario Ferrigno, Marianna Minnetti, Bianca Pellegrini, Andrea M. Isidori, Andrea Lenzi, Mariacarolina Salerno, Marco Cappa, Li Chan, Maria Cristina De Martino, Martin O. Savage
Summary: Adrenal insufficiency is a severe endocrine disorder characterized by insufficient secretion of glucocorticoid and/or mineralocorticoid due to impaired adrenal function or inadequate adrenal stimulation. This review focuses on rare genetic causes of primary adrenal insufficiency with isolated glucocorticoid or combined glucocorticoid and mineralocorticoid deficiencies, as well as rare syndromes of isolated mineralocorticoid deficiency. The diagnosis of these rare genetic forms of pediatric adrenal insufficiency is challenging due to their clinical heterogeneity and rarity, and this review aims to provide an overview of their genetic and clinical features, as well as diagnostic and therapeutic approaches.
REVIEWS IN ENDOCRINE & METABOLIC DISORDERS
(2023)
Article
Public, Environmental & Occupational Health
R. Asaad Baksh, Sarah E. Pape, Li F. Chan, Aisha A. Aslam, Martin C. Gulliford, Andre Strydom
Summary: This study comprehensively estimated the risk of multiple morbidity across the lifespan in people with Down syndrome and identified syndrome-specific health conditions. The results showed that people with Down syndrome had an increased risk of dementia, hypothyroidism, epilepsy, and haematological malignancy, while asthma, cancer, ischaemic heart disease, and hypertension were less frequent. Compared to people with other intellectual disabilities, people with Down syndrome had higher risks of dementia, hypothyroidism, obstructive sleep apnoea, and haematological malignancy, with reduced rates for a third of conditions. The morbidities in Down syndrome could be categorized based on age-related incidence trajectories and clustered into typical syndromic conditions, cardiovascular diseases, autoimmune disorders, and mental health conditions.
LANCET PUBLIC HEALTH
(2023)
Article
Endocrinology & Metabolism
Federica Buonocore, Avinaash Maharaj, Younus Qamar, Katrin Koehler, Jenifer P. Suntharalingham, Li F. Chan, Bruno Ferraz-de-Souza, Claire R. Hughes, Lin Lin, Rathi Prasad, Jeremy Allgrove, Edward T. Andrews, Charles R. Buchanan, Tim D. Cheetham, Elizabeth C. Crowne, Justin H. Davies, John W. Gregory, Peter C. Hindmarsh, Tony Hulse, Nils P. Krone, Pratik Shah, M. Guftar Shaikh, Catherine Roberts, Peter E. Clayton, Mehul T. Dattani, N. Simon Thomas, Angela Huebner, Adrian J. Clark, Louise A. Metherell, John C. Achermann
Summary: Genetic causes of primary adrenal insufficiency in children and young people were investigated in a cohort of 155 individuals in the UK, with 66.5% receiving a genetic diagnosis. Pathogenic variants were identified in 11 genes, highlighting the importance of genetic testing in defining the cause of PAI. Age at presentation, treatment, ancestral background, and birth weight can provide diagnostic clues, but genetic testing is often necessary for accurate diagnosis.
JOURNAL OF THE ENDOCRINE SOCIETY
(2021)