Review
Immunology
Jianan Zhao, Kai Wei, Ping Jiang, Cen Chang, Lingxia Xu, Linshuai Xu, Yiming Shi, Shicheng Guo, Dongyi He
Summary: In this review, the role of G-protein-coupled receptors (GPCRs) in the mechanisms of rheumatoid arthritis (RA) is discussed, and the latest clinical trials on GPCR targeting are summarized, providing a theoretical basis and guidance for the development of innovative GPCR-based clinical drugs for RA.
FRONTIERS IN IMMUNOLOGY
(2022)
Article
Endocrinology & Metabolism
Yuan Ma, Nicola Murgia, Yu Liu, Zixuan Li, Chaweewan Sirakawin, Ruslan Konovalov, Nikolai Kovzel, Yang Xu, Xuejia Kang, Anshul Tiwari, Patrick Malonza Mwangi, Donglei Sun, Holger Erfle, Witold Konopka, Qingxuan Lai, Syeda Sadia Najam, Ilya A. Vinnikov
Summary: This study aimed to identify non-coding genes that regulate metabolic function in mature neurons and found that miR-29a protects against insulin resistance obesity, hyperphagia, decreased energy expenditure, and obesity. The miR-29 family was identified as a key regulator of the PI3K-Akt-mTOR pathway.
MOLECULAR METABOLISM
(2022)
Review
Cell Biology
Tiemin Liu, Yong Xu, Chun-Xia Yi, Qingchun Tong, Dongsheng Cai
Summary: This review highlights the link between brain dysfunction and genetic mutations, sex, brain inflammation, microbiota, and stress as causes of whole-body pathophysiology. Studies suggest that dysfunction in the brain's perception and processing of internal and external cues can have profound effects on metabolism and other physiological functions.
Article
Chemistry, Multidisciplinary
Yi Zhang, Yangyang Zhu, Jinghui Wang, Li Jin, Mingwei Guo, Liwei Chen, Lina Zhang, Yangyang Li, Baocheng Wan, Rong Zhang, Weiping Jia, Cheng Hu
Summary: Nrg4 is an adipose tissue-enriched factor that regulates glucose and lipid metabolism and is closely associated with obesity. It acts on ErbB4 in the hypothalamus, excites PVN neurons, and influences energy balance. Its effects on reducing obesity are mediated through ErbB4-mediated excitation of Oxt release from Oxt neurons.
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)
Article
Biochemistry & Molecular Biology
Stephane Leon, Agnes Nadjar, Carmelo Quarta
Summary: Diet-induced obesity can result from dysregulated activity of hypothalamic neuronal circuits, potentially due to maladaptive communication between neurons and microglial cells. This interaction, crucial for the brain's orchestration of metabolic needs, may become detrimental under prolonged metabolic stress, leading to overfeeding, weight gain, and metabolic disturbances.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Biology
Mengyao Wu, Tak-Ho Lo, Liping Li, Jia Sun, Chujun Deng, Ka-Ying Chan, Xiang Li, Steve Ting-Yuan Yeh, Jimmy Tsz Hang Lee, Pauline Po Yee Lui, Aimin Xu, Chi-Ming Wong
Summary: This study found that adhesion G protein-coupled receptor F1 (Adgrf1) regulates hepatic lipid metabolism by controlling the expression of stearoyl-coA desaturase 1 (Scd1). The downregulation of Adgrf1 expression in the livers of obese subjects may serve as a protective mechanism to prevent the excessive accumulation of fat. These findings not only reveal a new mechanism for the progression of non-alcoholic fatty liver disease (NAFLD), but also propose a novel therapeutic approach to combat NAFLD by targeting Adgrf1.
Review
Pharmacology & Pharmacy
Kate F. Byrne, Ajay Pal, James F. Curtin, John C. Stephens, Gemma K. Kinsella
Summary: The focus of the review is on G-protein-coupled receptor (GPCR) targets, with chemokine, cannabinoid, and dopamine receptors showing promise. Further research is needed on potential targets such as MC4R, adhesion receptors, LPA, and Smo receptors to develop new drug-screening strategies for safe and effective GBM therapies.
DRUG DISCOVERY TODAY
(2021)
Review
Biochemistry & Molecular Biology
Dekel David, Ziv Bentulila, Merav Tauber, Yair Ben-Chaim
Summary: GPCRs are involved in signal transduction processes, and although they span the cell membrane, they have not been considered to be regulated by membrane potential. Recent studies, however, have shown that several GPCRs are voltage regulated. This review discusses the advances in understanding the voltage dependence of GPCRs, the suggested molecular mechanisms, and the possible physiological roles.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Biology
Ramon Cierco Jimenez, Nil Casajuana-Martin, Adrian Garcia-Recio, Lidia Alcantara, Leonardo Pardo, Mercedes Campillo, Angel Gonzalez
Summary: The study analyzed 119,069 natural variants in human olfactory receptors, revealing a significant diversity of natural variations in the olfactory gene repertoire between individuals and populations, with a considerable number of changes occurring at the structurally conserved regions. Mutations in positions linked to the conserved GPCR activation mechanism were highlighted, which could imply phenotypic variation in olfactory perception.
Article
Biochemistry & Molecular Biology
Laura Lemel, Katarzyna Niescierowicz, M. Dolores Garcia-Fernandez, Leonardo Darre, Thierry Durroux, Marta Busnelli, Mylene Pezet, Fabrice Rebeille, Juliette Jouhet, Bernard Mouillac, Carmen Domene, Bice Chini, Vadim Cherezov, Christophe J. Moreau
Summary: The study revealed a stable binding of cholesterol molecules to OXTR in the presence of orthosteric ligands, leading to a positive cross-regulation between cholesterol and orthosteric ligands, which preserves the activity of the receptor in cholesterol-depleted membranes.
JOURNAL OF LIPID RESEARCH
(2021)
Review
Pharmacology & Pharmacy
Sergi Ferre, Francisco Ciruela, Carmen W. Dessauer, Javier Gonzalez-Maeso, Terence E. Hebert, Ralf Jockers, Diomedes E. Logothetis, Leonardo Pardo
Summary: The study proposes the concept of GPCR-effect assemblies (GEMMAs), which are pre-assembled before receptor activation and allow more efficient interactions between specific signaling components. This offers an alternative model to the conventional collision coupling model and explains the differential properties of GPCRs in different cellular environments.
PHARMACOLOGY & THERAPEUTICS
(2022)
Review
Chemistry, Multidisciplinary
Xin-heng He, Chong-zhao You, Hua-liang Jiang, Yi Jiang, H. Eric Xu, Xi Cheng
Summary: G protein-coupled receptors (GPCRs) are important drug targets that play crucial roles in various physiological processes. Although extensive efforts have been made in the field of structural biology, a significant number of GPCR structures remain unsolved due to their structural instability. Recently, AlphaFold2 has been developed as a tool to predict the structure models of GPCRs and other functionally important proteins. However, our evaluation reveals several differences between the predicted models and experimental structures, such as the assembly of domains, shape of ligand-binding pockets, and conformation of binding interfaces. These differences hinder the use of predicted structure models in functional studies and structure-based drug design, where reliable high-resolution structural information is required.
ACTA PHARMACOLOGICA SINICA
(2023)
Article
Biochemistry & Molecular Biology
Wojciech Pietrus, Rafal Kurczab, Dagmar Stumpfe, Andrzej J. Bojarski, Juergen Bajorath
Summary: The study showed that introducing fluorine can significantly increase ligand potency, but the effect of fluorination on affinity varies depending on the fluorination position. Fluorination of the aromatic ring at the ortho position is favorable for potency enhancement, while fluorination of aliphatic fragments more often leads to a decrease in biological activity.
Article
Cell Biology
Saeed Al Mahri, Meshail Okla, Mamoon Rashid, Shuja Shafi Malik, Jahangir Iqbal, Maria Al Ibrahim, Ghida Dairi, Amer Mahmood, Manikandan Muthurangan, Ahmed Yaqinuddin, Sameer Mohammad
Summary: G protein-coupled receptors (GPCRs) play important roles in adipose tissue, with their expression being influenced by adipocyte differentiation and obesity. In mouse adipose tissue, 292 and 271 GPCRs were detected in white and brown adipose tissue, respectively, with some GPCRs being specific to each tissue type. The expression of numerous GPCRs was also identified in subcutaneous adipose tissue from human subjects and was altered in obesity and high-fat diet conditions. These GPCRs could have significant implications for adipose metabolism and serve as valuable resources for obesity and metabolic research.
Article
Immunology
Albina F. Ramalho, Bruna Bombassaro, Nathalia R. Dragano, Carina Solon, Joseane Morari, Milena Fioravante, Roberta Barbizan, Licio A. Velloso, Eliana P. Araujo
JOURNAL OF NEUROINFLAMMATION
(2018)
Article
Biochemistry & Molecular Biology
Milena Fioravante, Bruna Bombassaro, Albina F. Ramalho, Rodrigo F. de Moura, Roberta Haddad-Tovolli, Carina Solon, Nathalia R. Dragano, Jean F. Vettorazzi, Rodrigo S. Gaspar, Eduardo R. Ropelle, Everardo M. Carneiro, Joseane Morari, Licio A. Velloso
BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR BASIS OF DISEASE
(2019)
Review
Neurosciences
Nathalia R. V. Dragano, Johan Ferno, Carlos Dieguez, Miguel Lopez, Edward Milbank
Editorial Material
Endocrinology & Metabolism
Nathalia Dragano, Edward Milbank, Miguel Lopez
MOLECULAR METABOLISM
(2020)
Article
Neurosciences
Rodrigo S. Carraro, Guilherme A. Nogueira, Davi Sidarta-Oliveira, Rodrigo S. Gaspar, Nathalia R. Dragano, Joseane Morari, Vanessa C. D. Bobbo, Eliana P. Araujo, Natalia F. Mendes, Ariane M. Zanesco, Natalia Tobar, Celso D. Ramos, Jessica M. Toscaro, Marcio C. Bajgelman, Licio A. Velloso
Summary: NHLH2 is a hypothalamic transcription factor that plays a role in energy homeostasis and obesity. Overexpression of NHLH2 in mice can prevent and reduce obesity by affecting caloric intake.
JOURNAL OF NEUROSCIENCE
(2021)
Article
Nutrition & Dietetics
Valentina Capelli, Carmen Grijota-Martinez, Nathalia R. V. Dragano, Eval Rial-Pensado, Johan Ferno, Ruben Nogueiras, Jens Mittag, Carlos Dieguez, Miguel Lopez
Summary: This study used two different models of peripherally induced hyperthyroidism to assess the metabolic effects of peripheral TH treatment. The results showed that peripheral TH treatment affected various aspects of metabolism and induced changes in TH concentrations within the hypothalamus, indicating a central regulatory role in energy balance. Additionally, there was a shift in lipid metabolism from white adipose tissue accumulation to brown adipose tissue fueling, suggesting a complex interplay between central and peripheral effects of TH in the context of hyperthyroidism.
Article
Medicine, Research & Experimental
Ferran Comas, Ramon Diaz-Trelles, Aleix Gavalda-Navarro, Edward Milbank, Nathalia Dragano, Samantha Moron-Ros, Rajesh Mukthavaram, Jessica Latorre, Francisco Ortega, Maria Arnoriaga-Rodriguez, Nuria Oliveras-Canellas, Wifredo Ricart, Priya P. Karmali, Kiyoshi Tachikawa, Pad Chivukula, Francesc Villarroya, Marta Giralt, Miguel Lopez, Jose Manuel Fernandez-Real, Jose Maria Moreno-Navarrete
Summary: This study found that plasma lipopolysaccharide-binding protein (LBP) levels are associated with fat mass and leptin levels in obese women, but not in obese men. Downregulation of LBP in mice resulted in reduced weight, fat mass, and leptin gain in females after a high-fat and high-sucrose diet, while increased expression of adipogenic and thermogenic genes in visceral adipose tissue. Serum LPS levels were positively correlated with body weight and fat mass gain, and negatively correlated with markers of adipose tissue function only in female mice.
BIOMEDICINE & PHARMACOTHERAPY
(2022)
Article
Endocrinology & Metabolism
Robert Haddad Tovolli, Joseane Morari, Roberta Barbizan, Vanessa C. Bobbo, Rodrigo S. Carraro, Carina Solon, Nathalia R. Dragano, Marcio A. Torsoni, Eliana P. Araujo, Licio A. Velloso
Summary: Maternal obesity is a significant risk factor for obesity, cardiovascular, and metabolic diseases in offspring. It leads to inflammation in the hypothalamus of the offspring, affecting the function of neurons that regulate food intake and energy expenditure. Maternal obesity-induced structural and functional damage to the offspring's hypothalamic BBB, but breastfeeding by lean mothers can partially reverse these effects.
AMERICAN JOURNAL OF PHYSIOLOGY-ENDOCRINOLOGY AND METABOLISM
(2023)
Article
Pharmacology & Pharmacy
Edward Milbank, Ramon Diaz-Trelles, Nathalia Dragano, Jessica Latorre, Rajesh Mukthavaram, Jordi Mayneris-Perxachs, Francisco Ortega, Massimo Federici, Remy Burcelin, Priya P. Karmali, Kiyoshi Tachikawa, Pad Chivukula, Miguel Lopez, Jose Manuel Fernandez-Real, Jose Maria Moreno-Navarrete
Summary: Decreasing liver LBP levels can exacerbate oxidative stress and inflammation in the liver, further aggravating the progression of non-alcoholic steatohepatitis (NASH).
PHARMACOLOGICAL RESEARCH
(2023)
Review
Biochemistry & Molecular Biology
Jiri Lindovsky, Zuzana Nichtova, Nathalia R. V. Dragano, David Pajuelo Reguera, Jan Prochazka, Helmut Fuchs, Susan Marschall, Valerie Gailus-Durner, Radislav Sedlacek, Martin Hrabe de Angelis, Jan Rozman, Nadine Spielmann
Summary: Cardiovascular diseases have a high mortality rate globally and pose a significant burden on health care systems. The International Mouse Phenotyping Consortium (IMPC) utilizes mouse models to study cardiovascular diseases and aims to target each protein-coding gene to examine multiple organ systems. This review discusses the recent advances of the IMPC in cardiac research, focusing on the diagnostic requirements for high-throughput electrocardiography and transthoracic echocardiography in mice. Additionally, it explores the relationship between metabolism and the heart, highlighting the phenotypes that emerge in knockout mice for certain genes and identifying novel loss-of-function genes affecting both metabolism and the cardiovascular system.
Article
Biochemistry & Molecular Biology
Howard T. Jacobs, Marten Szibor, Birgit Rathkolb, Patricia da Silva-Buttkus, Juan Antonio Aguilar-Pimentel, Oana V. Amarie, Lore Becker, Julia Calzada-Wack, Nathalia Dragano, Lillian Garrett, Raffaele Gerlini, Sabine M. Hoelter, Tanja Klein-Rodewald, Markus Kraiger, Stefanie Leuchtenberger, Susan Marschall, Manuela A. Oestereicher, Kristina Pfannes, Adrian Sanz-Moreno, Claudia Seisenberger, Nadine Spielmann, Claudia Stoeger, Wolfgang Wurst, Helmut Fuchs, Martin Hrabe de Angelis, Valerie Gailus-Durner
Summary: The alternative oxidase (AOX) can delay the onset and progression of respiratory-chain diseases, but it does not provide long-term benefit.
BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR BASIS OF DISEASE
(2023)
Article
Endocrinology & Metabolism
Edward Milbank, Nathalia R. V. Dragano, Ismael Gonzalez-Garcia, Marcos Rios Garcia, Veronica Rivas-Limeres, Liliana Perdomo, Gregory Hilairet, Francisco Ruiz-Pino, Patricia Mallegol, Donald A. Morgan, Ramon Iglesias-Rey, Cristina Contreras, Luisa Vergori, Juan Cunarro, Begona Porteiro, Aleix Gavalda-Navarro, Rebecca Oelkrug, Anxo Vidal, Juan Roa, Tomas Sobrino, Francesc Villarroya, Carlos Dieguez, Ruben Nogueiras, Cristina Garcia-Caceres, Manuel Tena-Sempere, Jens Mittag, M. Carmen Martinez, Kamal Rahmouni, Ramaroson Andriantsitohaina, Miguel Lopez
Summary: Milbank et al. demonstrate that targeted delivery of AMPK alpha 1 in SF1 neurons of the VMH using small extracellular vesicles can lead to weight loss through increased brown adipose tissue thermogenesis, independent of feeding.
Review
Neurosciences
Nathalia R. Dragano, Johan Ferno, Carlos Dieguez, Miguel Lopez, Edward Milbank
Article
Chemistry, Medicinal
Andressa Mara Baseggio, Carla Evelyn Coimbra Nunez, Nathalia Romanelli Vicente Dragano, Celina Almeida Lamas, Patricia Aparecida de Campos Braga, Sabrina Alves Lenquiste, Felix Guillermo Reyes Reyes, Valeria Helena Alves Cagnon, Mario Roberto Marostica Junior
Article
Neurosciences
Yang He, Jun Tang, Meng Zhang, Junjie Ying, Dezhi Mu
Summary: This study investigated the protective effects and mechanisms of human placenta derived mesenchymal stem cells (hPMSCs) transplantation in a rat model of hypoxic-ischemic encephalopathy (HIE). The results showed that hPMSCs transplantation reduced apoptosis and improved long-term neurological prognosis. Furthermore, the downregulation of Sema 3A/NRP-1 expression and activation of the PI3K/Akt/mTOR signaling pathway played a key role in the protective effects of hPMSCs.
Article
Neurosciences
Emily L. Isenstein, Edward G. Freedman, Jiayi Xu, Ian A. DeAndrea-Lazarus, John J. Foxe
Summary: This study evaluated electrophysiological discrimination of parametric somatosensory stimuli in healthy young adults to understand how the brain processes the duration of tactile information. The results showed that participants did not electrophysiologically discriminate between 100 and 115 ms, but they exhibited distinct electrophysiological responses when the deviant stimuli were 130, 145, and 160 ms. These findings contribute to a better understanding of tactile sensitivity in different clinical conditions.
Article
Neurosciences
Juliana R. Souza, Ludmila Lima-Silveira, Daniela Accorsi-Mendonca, Benedito H. Machado
Summary: This study demonstrates that A2A receptors play a crucial role in modulating synaptic transmission in the NTS neurons and are required for the enhancement of glutamatergic transmission observed under short-term sustained hypoxia conditions.
Article
Neurosciences
Miki Hashizume, Rina Ito, Rie Suge, Yasushi Hojo, Gen Murakami, Takayuki Murakoshi
Summary: The basolateral amygdaloid complex (BLA) is closely involved in the formation of emotional memories, including both aversive memory and contextual fear memory. Acute sleep deprivation (SD) disrupts the acquisition of tone-associated fear memory in juvenile rats, but has no significant effect on contextual fear memory. Slow network oscillation in the amygdala contributes to the formation of amygdala-dependent fear memory in relation to sleep.
Article
Neurosciences
Qunxian Wang, Shipeng Guo, Dongjie Hu, Xiangjun Dong, Zijun Meng, Yanshuang Jiang, Zijuan Feng, Weihui Zhou, Weihong Song
Summary: GSDME plays a crucial role in the pathogenesis of Alzheimer's disease by regulating the switch from apoptosis to pyroptosis and participating in neuroinflammatory response. Knockdown of GSDME has been shown to improve cognitive impairments, indicating that GSDME could be a therapeutic target for Alzheimer's disease.