Review
Pharmacology & Pharmacy
Vanni Caruso, Mariachiara Zuccarini, Patrizia Di Iorio, Ishaq Muhammad, Maurizio Ronci
Summary: This review discusses the molecular mechanisms leading to changes in feeding behavior within hypothalamic neurons following purinergic receptor activation, emphasizes the importance of purinergic signaling in metabolic homeostasis, and explores the possibility of targeting its receptors for therapeutic purposes.
FRONTIERS IN PHARMACOLOGY
(2021)
Article
Multidisciplinary Sciences
Takefumi Kimura, Sai P. Pydi, Lei Wang, Dhanush Haspula, Yinghong Cui, Huiyan Lu, Gabriele M. Koenig, Evi Kostenis, Gregory R. Steinberg, Oksana Gavrilova, Juergen Wess
Summary: This study found that by activating adipocyte G(q) signaling, the increased lipolysis in obese individuals can be prevented, leading to improved glucose and lipid homeostasis. This has important implications for the development of novel anti-diabetic drugs based on GPCR.
NATURE COMMUNICATIONS
(2022)
Article
Multidisciplinary Sciences
Karol Cieminski, Damian Jozef Flis, Katarzyna Dzik, Jan Jacek Kaczor, Emilia Czyrko, Malgorzata Halon-Golabek, Mariusz Roman Wieckowski, Jedrzej Antosiewicz, Wieslaw Ziolkowski
Summary: The study found that swim training can reverse muscle atrophy in ALS mice, shedding light on potential practical implications for combating muscle wasting diseases related to ALS.
SCIENTIFIC REPORTS
(2021)
Article
Cell Biology
Song-Hua Hu, Xia-Di He, Ji Nie, Jun-Li Hou, Jiang Wu, Xiao-Yan Liu, Yun Wei, Hui-Ru Tang, Wen-Xing Sun, Shu-Xian Zhou, Yi-Yuan Yuan, Yan-Peng An, Guo-Quan Yan, Yan Lin, Peng-Cheng Lin, Jean J. Zhao, Ming-Liang Ye, Jian-Yuan Zhao, Wei Xu, Shi-Min Zhao
Summary: This study reveals that docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA) regulate cell signaling pathways by modifying specific proteins, and identifies the underlying mechanisms of their effects on the PI3K-AKT signaling pathway.
Article
Agriculture, Dairy & Animal Science
Yoshimitsu Ouchi, Yoshinori Komaki, Kensuke Shimizu, Natsuki Fukano, Toshihisa Sugino, Jun-Ichi Shiraishi, Vishwajit S. Chowdhury, Takashi Bungo
Summary: Fructose and glucose have different effects on food intake and metabolism in the body. Fructose administration does not suppress feeding behavior and does not increase blood glucose and insulin levels as glucose administration does. The expression of genes related to energy regulation in the hypothalamus is affected by glucose treatment in fasted chicks.
Article
Biology
Ahmad F. Alghanem, Javier Abello, Joshua M. Maurer, Ashutosh Kumar, Chau My Ta, Susheel K. Gunasekar, Urooj Fatima, Chen Kang, Litao Xie, Oluwaseun Adeola, Megan Riker, Macaulay Elliot-Hudson, Rachel A. Minerath, Chad E. Grueter, Robert F. Mullins, Amber N. Stratman, Rajan Sah
Summary: The LRRC8A-dependent volume-regulated anion channel (VRAC) is crucial for regulating vascular function and is particularly important in the context of type 2 diabetes (T2D). LRRC8A modulates endothelial cell function in the vascular system by regulating signaling pathways such as AKT-eNOS.
Article
Biochemistry & Molecular Biology
Medha Sharma, Chinmoy Sankar Dey
Summary: The study aimed to determine the role of Akt isoforms in insulin signaling and resistance in neuronal cells. The findings suggest that Akt2 plays a major role in regulating glucose uptake under insulin-sensitive conditions, while Akt1 and Akt3 have compensatory roles in neuronal insulin signaling, glucose uptake, and insulin-resistance. The differential translocation of Akt isoforms to the plasma membrane post-insulin stimulation is a key factor in determining Akt isoform specificity.
CELLULAR AND MOLECULAR LIFE SCIENCES
(2021)
Editorial Material
Oncology
Aaron M. Hosios, Brendan D. Manning
Summary: Research has deepened the understanding of oncogenic control of metabolism, particularly glycolysis. Current focus is on understanding the benefits and risks associated with glycolytic metabolism, and finding inhibitors that could be clinically beneficial for targeting glycolytic cancer cells.
Article
Multidisciplinary Sciences
Yan Wang, Chenzhong Jin, Yuzhen Yi, Yihong Hu, Xuefeng Han, Zhiliang Tan, Zheng Wang, Jinhe Kang
Summary: This study aimed to investigate the effects of dietary rumen-protected glucose (RPG) on reproductive hormones and the mTOR/AKT/PI3K pathway in the ovaries of postpartum dairy cows. The results showed that RPG supplementation increased LH, E2, and P4 levels in the blood of cows on day 14 after calving. It also upregulated the expression of hormone receptors and the mTOR/AKT pathway in the ovaries. These findings suggest that RPG may have a beneficial effect on the recovery of ovarian activity in post-calving dairy cows.
SCIENTIFIC REPORTS
(2023)
Review
Multidisciplinary Sciences
Hamidreza Shaye, Benjamin Stauch, Cornelius Gati, Vadim Cherezov
Summary: GABA(B) receptors play a crucial role in inhibitory neurotransmission in the brain, modulating neuronal signaling and being linked to various neurological disorders. Recent cryo-EM studies have provided detailed insights into the activation mechanism of GABA(B) receptors, offering potential for the discovery of new therapeutic drugs and neuromodulators. The structures of the receptor in different conformational states and bound to various ligands contribute to a comprehensive understanding of the receptor's activation process.
Article
Biology
Pradeep Bhandari, David Vandael, Diego Fernandez-Fernandez, Thorsten Fritzius, David Kleindienst, Cihan Onal, Jacqueline Montanaro, Martin Gassmann, Peter Jonas, Akos Kulik, Bernhard Bettler, Ryuichi Shigemoto, Peter Koppensteiner
Summary: The study found that KCTD8 and KCTD12b directly bind to Cav2.3 and co-localize in the rostral IPN. These KCTDs modulate synaptic strength by regulating Cav2.3-mediated release, independent of GBR activation.
Article
Multidisciplinary Sciences
Qinbo Cai, Wolong Zhou, Wei Wang, Bingning Dong, Dong Han, Tao Shen, Chad J. Creighton, David D. Moore, Feng Yang
Summary: The study revealed that MAPK6 activates AKT independently of mTORC2, potentially providing a major resistance pathway in cancer. Inhibiting MAPK6 sensitized cancer cells to mTOR kinase inhibitors. Overexpression of MAPK6 is associated with decreased overall survival in various cancer patients.
Article
Medicine, Research & Experimental
Helen E. Burston, Oliver A. Kent, Laudine Communal, Molly L. Udaskin, Ren X. Sun, Kevin R. Brown, Euihye Jung, Kyle E. Francis, Jose La Rose, Joshua Lowitz, Ronny Drapkin, Anne-Marie Mes-Masson, Robert Rottapel
Summary: Relaxin and its associated GPCR RXFP1 form an autocrine signaling loop essential for ovarian cancer in vivo tumorigenesis, cell proliferation, and viability. Relaxin signaling activates expression of prooncogenic pathways, and inflammatory cytokines can activate Relaxin transcription.
JOURNAL OF CLINICAL INVESTIGATION
(2021)
Article
Developmental Biology
Jose Esteban-Collado, Montserrat Corominas, Florenci Serras
Summary: The study showed that in Drosophila wing, PI3K Akt signaling is crucial for Ask1 to activate p38, but not JNK. Nutrient restriction or mutations targeting specific residues of Drosophila Ask1 protein can block regeneration, which can be reversed by ectopic activation of p38.
Article
Multidisciplinary Sciences
Carly M. Darden, Srividya Vasu, Jordan Mattke, Yang Liu, Christopher J. Rhodes, Bashoo Naziruddin, Michael C. Lawrence
Summary: The study reveals that calcineurin and PI3K/AKT signaling pathways play important roles in maintaining beta-cell function, but prolonged exposure to stress or perturbation of these pathways may lead to beta-cell dedifferentiation and dysfunction.
Article
Endocrinology & Metabolism
Maria Elisa Mercau, Juan Salvador Calanni, Marcos Luis Aranda, Lilian Julia Caldareri, Ruth Estela Rosenstein, Esteban Martin Repetto, Cora Beatriz Cymeryng
JOURNAL OF PINEAL RESEARCH
(2019)
Article
Cell & Tissue Engineering
Mercedes Tome, Jan Tchorz, Martin Gassmann, Bernhard Bettler
STEM CELL RESEARCH
(2019)
Review
Pharmacology & Pharmacy
Thorsten Fritzius, Bernhard Bettler
BASIC & CLINICAL PHARMACOLOGY & TOXICOLOGY
(2020)
Article
Chemistry, Medicinal
Vita Sereikaite, Thorsten Fritzius, Vikram B. Kasaragod, Nicole Bader, Hans M. Maric, Hermann Schindelin, Bernhard Bettler, Kristian Stromgaard
JOURNAL OF MEDICINAL CHEMISTRY
(2019)
Article
Biochemistry & Molecular Biology
Manuel Winkler, Siladitta Biswas, Stefan M. Berger, Moritz Kuechler, Laurens Preisendoerfer, Myeongjeong Choo, Simon Fruh, Pascal D. Rem, Thomas Enkel, Bernd Arnold, Dorde Komljenovic, Carsten Sticht, Sergij Goerdt, Bernhard Bettler, Oliver von Bohlen und Halbach, Dusan Bartsch, Cyrill Geraud
MOLECULAR PSYCHIATRY
(2020)
Article
Clinical Neurology
Alejandro Martin-Belmonte, Carolina Aguado, Rocio Alfaro-Ruiz, Ana Esther Moreno-Martinez, Luis de la Ossa, Jose Martinez-Hernandez, Alain Buisson, Simon Frueh, Bernhard Bettler, Ryuichi Shigemoto, Yugo Fukazawa, Rafael Lujan
Article
Neurosciences
Ruth C. Werthmann, Manuel Tzouros, Jens Lamerz, Angelique Augustin, Thorsten Fritzius, Luca Trovo, Michal Stawarski, Adi Raveh, Catherine Diener, Christophe Fischer, Martin Gassmann, Lothar Lindemann, Bernhard Bettler
Summary: Recent studies have shown that mGlu1 and mGlu5 form functional heterodimers in the brain, exhibiting symmetric signal transduction where both protomers need to reach an active conformation for full receptor activity. This highlights differences in the signaling transduction of heterodimeric mGluRs that influence allosteric modulation.
Article
Neurosciences
Alessandra Porcu, Rafaela Mostallino, Valeria Serra, Miriam Melis, Valeria Sogos, Sarah Beggiato, Luca Ferraro, Fabrizio Manetti, Beatrice Gianibbi, Bernhard Bettler, Federico Corelli, Claudia Mugnaini, M. Paola Castelli
Summary: This study characterized the negative allosteric modulator COR758 for GABA(B) receptors, showing its potential as a therapeutic candidate by inhibiting G protein signaling. COR758 may serve as a scaffold for developing additional NAMs for therapeutic intervention by interacting with an allosteric binding site of GABA(B) receptors.
Article
Multidisciplinary Sciences
Li-Pao Fang, Na Zhao, Laura C. Caudal, Hsin-Fang Chang, Renping Zhao, Ching-Hsin Lin, Nadine Hainz, Carola Meier, Bernhard Bettler, Wenhui Huang, Anja Scheller, Frank Kirchhoff, Xianshu Bai
Summary: Early disruption of GABA/TNFSF12 signaling between interneurons and oligodendrocyte precursor cells impairs prefrontal cortical network activity and social cognitive behavior later in life. The study identifies a bidirectional communication pathway between fast spiking interneurons and oligodendrocyte precursor cells that determines the density and function of interneurons in the developing prefrontal cortex. Interruption of this signaling results in reduced myelination, hypoactivity of interneurons, changes in cortical network activities, and impaired social cognitive behavior. Glial transmitter receptors play a crucial role in fine-tuning distinct brain functions.
NATURE COMMUNICATIONS
(2022)
Article
Genetics & Heredity
Maria Lucia Cediel, Michal Stawarski, Xavier Blanc, Lenka Noskova, Martin Magner, Konrad Platzer, Janina Gburek-Augustat, Dustin Baldridge, John N. Constantino, Emmanuelle Ranza, Bernhard Bettler, Stylianos E. Antonarakis
Summary: GABA(B) receptors are responsible for neuronal inhibition in the central nervous system. Variants in GABBR2 have been associated with certain phenotypes, while no phenotypes have been established for GABBR1 variants. This study identified four GABBR1 variants in individuals with motor and/or language delay, and functional characterization revealed their impact on GABA potency and efficacy, providing insights into disease severity and potential therapeutic strategies.
AMERICAN JOURNAL OF HUMAN GENETICS
(2022)
Article
Endocrinology & Metabolism
Noelia P. Di Giorgio, Marianne Bizzozzero-Hiriart, Pablo N. Surkin, Esteban Repetto, Maria M. Bonaventura, Florencia N. Tabares, Nadia S. Bourguignon, Ayelen Converti, Juan M. Riano Gomez, Bernhard Bettler, Victoria Lux-Lantos
Summary: GABA and Kisspeptin play critical roles in reproduction and metabolic control. A unique mouse lacking GABAB receptors in Kiss1 cells showed severe impairment in glucose homeostasis, which worsened with aging. These results reinforce the involvement of Kisspeptin in metabolic regulation and highlight the importance of GABA through GABAB receptors in the regulation of the peripheral pancreas Kisspeptin system.
AMERICAN JOURNAL OF PHYSIOLOGY-ENDOCRINOLOGY AND METABOLISM
(2023)
Article
Biology
Pascal Dominic Rem, Vita Sereikaite, Diego Fernandez-Fernandez, Sebastian Reinartz, Daniel Ulrich, Thorsten Fritzius, Luca Trovo, Salome Roux, Ziyang Chen, Philippe Rondard, Jean-Philippe Pin, Jochen Schwenk, Bernd Fakler, Martin Gassmann, Tania Rinaldi Barkat, Kristian Stromgaard, Bernhard Bettler
Summary: Amyloid-beta precursor protein (APP) regulates neuronal activity through the release of secreted APP (sAPP) acting at cell surface receptors. A 17 amino acid peptide (APP17) derived from APP binds to the extracellular sushi domain 1 (SD1) of GABA(B) receptors (GBRs). However, APP17 does not influence GBR activity in heterologous cells, indicating that sAPP exerts its neuronal effects through receptors other than GBRs.
Review
Biotechnology & Applied Microbiology
Mette Ishoy Rosenbaum, Louise S. Clemmensen, David S. Bredt, Bernhard Bettler, Kristian Stromgaard
NATURE REVIEWS DRUG DISCOVERY
(2020)
Article
Multidisciplinary Sciences
Taku Tsunekawa, Ryoichi Banno, Hiroshi Yaginuma, Keigo Taki, Akira Mizoguchi, Mariko Sugiyama, Takeshi Onoue, Hiroshi Takagi, Daisuke Hagiwara, Yoshihiro Ito, Shintaro Iwama, Motomitsu Goto, Hidetaka Suga, Bernhard Bettler, Hiroshi Arima
Article
Endocrinology & Metabolism
Esteban M. Repetto, Morena Wiszniewski, Ana L. Bonelli, Carolina V. Vecino, Camila Martinez Calejman, Pablo Arias, Cora B. Cymeryng
Article
Medicine, Research & Experimental
Yuwen Zhu, Yan Guo, Yujia Xue, Anqi Zhou, Ying Chen, Yifei Chen, Xiulian Miao, Fangqiao Lv
Summary: BRG1 plays an important role in HSC-myofibroblast transition and targeting it could be a reasonable strategy for liver fibrosis intervention.
Article
Medicine, Research & Experimental
Liu Ye, Beibei Liu, Jingling Huang, Xiaolin Zhao, Yuan Wang, Yungen Xu, Shuping Wang
Summary: Doublecortin-like kinase 1 (DCLK1) is a significant prooncogenic factor that is strongly associated with the malignant progression and clinical prognosis of various cancers. DCLK1 plays important roles in stem cell marker regulation, tumor cell reprogramming, and immune evasion. However, the exact biological functions of DCLK1, especially the disparities between its alpha- and beta-form transcripts in cancer progression, remain ambiguous.
Article
Medicine, Research & Experimental
Jiahui Yang, Xiaoyu Chen, Tianjing Liu, Yongyan Shi
Summary: This article reviews the role of bile acids in necrotizing enterocolitis (NEC) and their potential therapeutic value. The dysregulation of bile acids is associated with intestinal injury, and inflammatory factors in the liver also play a crucial role in regulating bile acid transport. The bile acid metabolic pathway is important for regulating intestinal microbiota, cell proliferation, and barrier protection.
Review
Medicine, Research & Experimental
Zhenzheng Zhu, Yuemiao Xu, Yuwei Xia, Xinru Jia, Yixin Chen, Yuyue Liu, Leyin Zhang, Hui Chai, Leitao Sun
Summary: Bile acid, as the final product of cholesterol breakdown, plays a complex regulatory and signaling role in human metabolism. Research suggests that it has the potential to enhance metabolism and regulate chronic metabolic diseases through various pathways. The interaction between bile acid and gut microbiota is also of great significance.
Article
Medicine, Research & Experimental
Xin He, Hong-Xu Zhou, Xian Fu, Kai-Di Ni, Ai-Zhi Lin, Ling-Tong Zhang, Hou-Hua Yin, Qing Jiang, Xue Zhou, Yi-Wen Meng, Jun-Yan Liu
Summary: DON exposure causes an increase in deoxycholic acid (DCA), which contributes to intestinal injury. DCA may be a potential therapeutic target for DON enterotoxicity.
Article
Medicine, Research & Experimental
Zhitao Wang, Heng Ma, Abdul Nasir, Sufang Liu, Zhisong Li, Feng Tao, Qian Bai
Summary: This study reveals the involvement of TET1-mediated epigenetic regulation in chronic TMJ pain through trigeminal TNF alpha signaling.
Article
Medicine, Research & Experimental
Lu Yu, Hao Ran, Yaru Lu, Qian Ma, Huan Huang, Weibin Liu
Summary: This study found that the HIF-1 alpha inhibitor BAY 87-2243 can alleviate the symptoms of the Experimental Autoimmune Myasthenia Gravis (EAMG) inflammation model. BAY 87-2243 can restore the balance of CD4(+)T cell subsets, reduce the production of pro-inflammatory cytokines, and act as both an immune imbalance regulator and anti-inflammatory.
Article
Medicine, Research & Experimental
Alex Peralvarez-Marin, Montse Sole, Judith Serrano, Alice Taddeucci, Belen Perez, Clara Penas, Gemma Manich, Marcel Jimenez, Pilar D'Ocon, Francesc Jimenez-Altayo
Summary: This study provides the first evidence that TRPV2 channels may modulate vascular tone by balancing opposing inputs from the endothelium and smooth muscle, leading to net vasodilation. The amplification of TRPV2 channel-induced activity by NO emphasizes the pathophysiological relevance of these findings.
Article
Medicine, Research & Experimental
Amin Ullah, Jing Zhao, Jiakun Li, Rajeev K. Singla, Bairong Shen
Summary: Gastric cancer is the fifth-most prevalent and second-most deadly cancer worldwide. Late onset of symptoms makes early detection important. CXC chemokines play an important role in the pathological process of gastric cancer, but their exact role in diagnosis and prognosis is not fully understood. Inhibiting CXC chemokines shows promise as a targeted therapy.
Article
Medicine, Research & Experimental
Menna S. Zeyada, Salma M. Eraky, Mamdouh M. El-Shishtawy
Summary: The current study demonstrates the prophylactic and antifibrotic effects of Trig against BLM-induced PF by targeting multiple signaling pathways. The combination of Trig and Pirf may be a promising approach to enhance Pirf's anti-fibrotic effect.