Article
Multidisciplinary Sciences
Brian Tenner, Jason Z. Zhang, Yonghoon Kwon, Veronica Pessino, Siyu Feng, Bo Huang, Sohum Mehta, Jin Zhang
Summary: FluoSTEPs is a novel class of biosensors that combines self-complementing split green fluorescent protein, CRISPR-mediated knock-in, and fluorescence resonance energy transfer technology to probe compartmentalized signaling dynamics in situ. It can simultaneously highlight endogenous microdomains and report domain-specific, real-time signaling events, including kinase activities, guanosine triphosphatase activation, and second messenger dynamics. FluoSTEPs have been shown to be useful in probing spatiotemporal regulation within endogenous signaling architectures, as demonstrated by a FluoSTEP for 3',5'-cyclic adenosine monophosphate (cAMP) revealing distinct cAMP dynamics within clathrin microdomains in response to stimulation of G protein-coupled receptors.
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)
Article
Biochemistry & Molecular Biology
Melissa Girard, Steve Dagenais Bellefeuille, Emilie Eiselt, Guillaume Arguin, Jean-Michel Longpre, Philippe Sarret, Fernand-Pierre Gendron
Summary: This study found that endosomal trafficking plays an important role in G protein-coupled receptor (GPCR) signaling. UDP selectively activates GPCR P2Y6 as a signaling molecule. The study found that MRS2693 and UDP have different effects on the internalization of the P2Y6 receptor, with MRS2693 inducing P2Y6 internalization through an independent caveolin-dependent mechanism. This study provides insights for the development of bias ligands that can influence P2Y6 signaling.
BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR CELL RESEARCH
(2023)
Review
Medicine, Research & Experimental
Juan Carlos Martinez-Morales, K. Helivier Solis, M. Teresa Romero-Avila, Guadalupe Reyes-Cruz, J. Adolfo Garcia-Sainz
Summary: G protein-coupled receptors (GPCRs) are membrane proteins that function as sensors and play significant roles in various physiological and pathological processes. This review provides an overview of the current understanding of the structure, signaling, internalization, and recycling of GPCRs.
ARCHIVES OF MEDICAL RESEARCH
(2022)
Article
Pharmacology & Pharmacy
Mark von Zastrow
Summary: Advances in proteomic methodologies based on quantitative mass spectrometry are revolutionizing pharmacology and experimental biology. This review focuses on the interplay between G protein-coupled receptor signaling and trafficking in the endocytic network, highlighting recent progress and challenges in elucidating the cellular basis of drug action using proteomic approaches.
MOLECULAR PHARMACOLOGY
(2021)
Review
Cell Biology
Ze-Qin Wen, Di Liu, Yi Zhang, Zi-Jun Cai, Wen-Feng Xiao, Yu-Sheng Li
Summary: G protein-coupled receptors (GPCRs) are important transmembrane receptor proteins that play crucial roles in the pathogenesis of osteoarthritis (OA). Current research indicates that targeting GPCRs could provide a novel therapeutic strategy for OA treatment.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2021)
Review
Endocrinology & Metabolism
Fanhua Wang, Mingyao Liu, Ning Wang, Jian Luo
Summary: This review discusses the role of G-protein coupled receptors (GPCRs) in osteoarthritis (OA), including the pathophysiological processes involved, preclinical and clinical trial data, and the challenges in developing therapies targeting GPCRs for OA.
FRONTIERS IN ENDOCRINOLOGY
(2022)
Review
Pharmacology & Pharmacy
Juan Carlos Martinez-Morales, M. Teresa Romero-Avila, Guadalupe Reyes-Cruz, Jesus Adolfo Garcia-Sainz
Summary: The phosphorylation and endosomal traffic of G protein-coupled receptors play a significant role in receptor responsiveness, cellular localization, and fate, with important implications in pharmacology and therapy.
MOLECULAR PHARMACOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Catherine A. Tindall, Kevin Moehlis, Inka Rapoehn, Sebastian Dommel, Veronika Riedl, Michael Schneekoenig, Corinna Hoefling, Steffen Rossner, Jan Stichel, Annette G. Beck-Sickinger, Juliane Weiner, John T. Heiker
Summary: This study reveals the uptake and degradation mechanism of Vaspin in adipocytes, and proposes the Vaspin-LRP1 axis as an important mediator of Vaspin effects not only in adipose tissue but also in other LRP1-expressing cells.
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
Chemistry, Medicinal
Joshua W. Conner, Daniel P. Poole, Manuela Jorg, Nicholas A. Veldhuis
Summary: This review addresses the key challenges, synthesis approaches, and structure-activity relationships in recent fluorescent small molecule studies for GPCRs, and discusses the advantages of using high-resolution GPCR structures to inform conjugation strategies.
FUTURE MEDICINAL CHEMISTRY
(2021)
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)
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
Oncology
Christian Dehlendorff, Louise Baandrup, Susanne K. Kjaer
Summary: The study based on a cohort of Danish women found that HPV vaccination before the age of 17 can reduce the risk of vulvar and vaginal high-grade squamous intraepithelial lesions. However, the effectiveness of vaccination was smaller for those vaccinated between the ages of 17-26.
JNCI-JOURNAL OF THE NATIONAL CANCER INSTITUTE
(2021)
Article
Obstetrics & Gynecology
Louise T. Thomsen, Susanne K. Kjaer, Christian Munk, Dorthe Ornskov, Marianne Waldstrom
Summary: Compared to cytology-based screening, HPV-based screening resulted in a 90% increase in CIN3+ detection but also led to a threefold increase in colposcopy referrals. The findings support the implementation of HPV-based screening in Denmark, but adjustments to screening algorithms may be necessary to reduce unnecessary colposcopy referrals.
ACTA OBSTETRICIA ET GYNECOLOGICA SCANDINAVICA
(2021)
Article
Immunology
Julie B. Hebnes, Christian Munk, Kirsten Frederiksen, Hans O. Joergensen, Thomas Iftner, Susanne K. Kjaer
Summary: Smoking was associated with increased odds of penile HPV infection in men from the general population in Denmark, while circumcision seemed to reduce the risk. Moreover, differences in viral susceptibility between circumcised and uncircumcised men were indicated by the results.
INTERNATIONAL JOURNAL OF STD & AIDS
(2021)
Article
Dermatology
Linn Freund, Susanne K. Kjaer, Sonia Guleria, Vanna Albieri, Anne-Marie Nybo Andersen, Kirsten Frederiksen, Allan Jensen
Summary: The study found that the use of fertility drugs was associated with a modestly increased risk of malignant melanoma, especially among women with fertility challenges. The specific types of fertility drugs were also found to be possibly linked to an increased risk of malignant melanoma, although the association did not reach statistical significance.
JOURNAL OF INVESTIGATIVE DERMATOLOGY
(2021)
Article
Oncology
Trille Kristina Kjaer, Ida Rask Moustsen-Helms, Vanna Albieri, Signe Benzon Larsen, Thea Helene Degett, Anne Tjonneland, Christoffer Johansen, Susanne K. Kjaer, Ismail Gogenur, Susanne Oksbjerg Dalton
Summary: This population-based prospective cohort study analyzed the risk of depression in colorectal cancer patients, finding a significantly elevated risk in the first year after cancer diagnosis which decreased over time. Identified risk factors included presence of comorbidities, advanced disease stage, and use of radiotherapy, while lifestyle factors and chemotherapy did not contribute to the increased risk.
Article
Endocrinology & Metabolism
K. Reinholdt, C. Munk, L. T. Thomsen, C. Dehlendorff, B. Carstensen, M. E. Jorgensen, S. K. Kjaer
Summary: A study in Denmark found that individuals with type 1 diabetes have higher incidence rates of genital warts compared to those without diabetes, across all age groups. This highlights the importance of HPV vaccination for young girls and boys with type 1 diabetes.
ACTA DIABETOLOGICA
(2022)
Article
Respiratory System
Daniel Ward, Sanne Gortz, Martin Thomson Ernst, Nynne Nyboe Andersen, Susanne K. Kjaer, Jesper Hallas, Steffen Christensen, Christian Fynbo Christiansen, Simone Bastrup Israelsen, Thomas Benfield, Anton Pottegard, Tine Jess
Summary: This nationwide cohort study in Denmark found that exposure to glucocorticoids is associated with increased risks of hospital admission and death in patients with COVID-19. Further research is needed to determine if altered doses of glucocorticoids are necessary for these patients.
EUROPEAN RESPIRATORY JOURNAL
(2022)
Article
Oncology
Tina Bech Olesen, Freja L. Sand, Gitte L. Aalborg, Christian Munk, Susanne K. Kjaer
Summary: Research in Denmark showed a gradual increase in high-grade penile intraepithelial neoplasia cases, while the 5-year relative survival rate of penile squamous cell carcinoma remained relatively stable. Increased exposure to HPV infection may have contributed to the rise in high-grade PeIN and penile SCC.
CANCER CAUSES & CONTROL
(2022)
Article
Oncology
Cecilie Dovey de la Cour, Christian Munk, Gitte Lerche Aalborg, Susanne Kruger Kjaer
Summary: The incidence of base-of-tongue/tonsillar cancer has increased in Denmark over the past 25 years, regardless of educational level and age group. In contrast, the trends for laryngeal cancer show social inequality, with a decrease in incidence among individuals with medium and high education, and an increase among those with low education.
Article
Gastroenterology & Hepatology
Rahma Elmahdi, Louise T. Thomsen, Aske T. Iversen, Kristine H. Allin, Susanne K. Kjaer, Tine Jess
Summary: This study aimed to assess the risk of genital warts (GW) in patients with inflammatory bowel disease (IBD). The results showed that IBD patients had a 33% increased risk of GW compared to the general population, and CD patients had a 13% increased risk of GW compared to UC. This risk was particularly observed in female IBD patients.
UNITED EUROPEAN GASTROENTEROLOGY JOURNAL
(2022)
Article
Oncology
Christoph Wohlmuth, Vladimir Djedovic, Susanne K. Kjaer, Allan Jensen, Rosalind Glasspool, Patricia Roxburgh, Anna DeFazio, Sharon E. Johnatty, Penelope M. Webb, Francesmary Modugno, Diether Lambrechts, Joellen M. Schildkraut, Andrew Berchuck, Liv Cecilie Vestrheim Thomsen, Line Bjorge, Estrid Hogdall, Claus K. Hogdall, Ellen L. Goode, Stacey J. Winham, Keitaro Matsuo, Beth Y. Karlan, Jenny Lester, Marc T. Goodman, Pamela J. Thompson, Tanja Pejovic, Marjorie J. Riggan, Katherine Lajkosz, Alicia Tone, Taymaa May
Summary: This study analyzed data from 176 women with low-grade serous ovarian cancer through a multi-center collaborative effort, revealing that elevated post-treatment CA-125 levels are significantly associated with poor survival, while FIGO staging and residual disease also impact patient outcomes.
Article
Oncology
Clarissa L. B. Frandsen, Allan Jensen, Frantz R. Poulsen, Maria Moller, Sofie Lindquist, Vanna Albieri, Bugge Nohr, Susanne K. Kjaer
Summary: This study aimed to investigate the association between fertility drugs and tumors of the central nervous system (CNS). The results showed no significant associations between most types of fertility drugs and CNS tumors, but further studies with longer follow-up time are necessary to draw accurate conclusions, particularly for premenopausal women.
CANCER CAUSES & CONTROL
(2022)
Article
Cell Biology
Feipeng Zhu, Lina Liu, Jie Li, Bing Liu, Qinglong Wang, Ruiying Jiao, Yongxin Xu, Lun Wang, Suhua Sun, Xiaoxuan Sun, Muhammad Younus, Changhe Wang, Tomas Hokfelt, Bo Zhang, Howard Gu, Zhi-Qing David Xu, Zhuan Zhou
Summary: This study demonstrates that cocaine directly increases the frequency of quantal NE release through regulation of NET and downstream PKC signaling, which modulates the activity of LC-NE neurons and cocaine-induced stimulant behavior.
Article
Oncology
Mathilde Gottschau, Susanne K. K. Kjaer, Jakob Hansen Viuff, Allan Jensen, Christian Munk, Annette Settnes, Lene Mellemkjaer
Summary: The results from this study indicate that removing the ovaries prior to cancer diagnosis through benign hysterectomy does not improve the prognosis of breast cancer.
BREAST CANCER RESEARCH AND TREATMENT
(2023)
Article
Oncology
Clarissa L. B. Frandsen, Pernille F. Svendsen, Bugge Nohr, Jakob H. Viuff, Thomas Maltesen, Susanne K. Kjaer, Allan Jensen
Summary: There is a potential association between polycystic ovary syndrome (PCOS) and epithelial ovarian tumors due to shared risk factors. However, previous studies have shown conflicting results and methodological limitations. A population-based cohort study in Denmark was conducted to investigate this association. While there was no overall association, postmenopausal women with PCOS had an increased risk of ovarian cancer and women with PCOS had an increased risk of serous borderline ovarian tumors compared to those without PCOS. Larger studies with longer follow-up are needed to confirm these findings.
INTERNATIONAL JOURNAL OF CANCER
(2023)
