Article
Chemistry, Multidisciplinary
Johannes Morstein, Giovanna Romano, Belinda E. Hetzler, Ambrose Plante, Caleb Haake, Joshua Levitz, Dirk Trauner
Summary: This study develops tools for optical control of serotonin receptors, providing a new method for studying receptor function. By constructing a repeatable and reversible optical control system, this study lays the foundation for extending photopharmacology to the serotonin receptor family.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2022)
Article
Multidisciplinary Sciences
Anat Levit Kaplan, Danielle N. Confair, Kuglae Kim, Ximena Barros-Alvarez, Ramona M. Rodriguiz, Ying Yang, Oh Sang Kweon, Tao Che, John D. McCorvy, David N. Kamber, James P. Phelan, Luan Carvalho Martins, Vladimir M. Pogorelov, Jeffrey F. DiBerto, Samuel T. Slocum, Xi-Ping Huang, Jain Manish Kumar, Michael J. Robertson, Ouliana Panova, Alpay B. Seven, Autumn Q. Wetsel, William C. Wetsel, John J. Irwin, Georgios Skiniotis, Brian K. Shoichet, Bryan L. Roth, Jonathan A. Ellman
Summary: Researchers successfully screened and synthesized molecules that can activate the 5-HT2A receptor using structure-based docking and optimization methods. These molecules exhibited potent antidepressant activity in mouse models without psychedelic effects.
Article
Multidisciplinary Sciences
Maxemiliano V. Vargas, Lee E. Dunlap, Chunyang Dong, Samuel J. Carter, Robert J. Tombari, Shekib A. Jami, Lindsay P. Cameron, Seona D. Patel, Joseph J. Hennessey, Hannah N. Saeger, John D. McCorvy, John A. Gray, Lin Tian, David E. Olson
Summary: Decreased dendritic spine density in the cortex is a common feature of neuropsychiatric diseases, and psychedelics have been found to promote cortical neuron growth. This study shows that intracellular 5-HT2A receptors mediate the plasticity-promoting effects of psychedelics, providing insight into the mechanisms behind their therapeutic effects. The findings suggest that targeting intracellular 5-HT2A receptors could be a potential therapeutic approach.
Article
Pharmacology & Pharmacy
Sean M. Collins, Christopher J. O'Connell, Evan L. Reeder, Sophia V. Norman, Kainat Lungani, Poornima Gopalan, Gary A. Gudelsky, Matthew J. Robson
Summary: Various forms of TBI are a leading cause of disability in the US, with the generation of neuropsychiatric complications such as depression and anxiety. This study found that mild TBI can lead to selective alterations in cortical 5-HT2A receptor signaling, which may be targeted for the development of pharmacotherapies to alleviate TBI-induced neuropsychiatric disorders.
FRONTIERS IN PHARMACOLOGY
(2022)
Article
Medicine, Research & Experimental
Bo Li, Jingjing Ye, Ruxia Liu, Lin Weng, Yangpo Cao, Shi Jia, Chunling Xu, Yingying Liu, Saifang Yan, Ming Zheng
Summary: The study revealed that PDCD5 is upregulated in the early stage of insulin resistance in skeletal muscle, providing protection by increasing the stability of IRS-1 through its interaction with MDM2.
Article
Biochemistry & Molecular Biology
Deepa Mathew, Julia Barillas-Cerritos, Ana Nedeljkovic-Kurepa, Mabel Abraham, Matthew D. Taylor, Clifford S. Deutschman
Summary: Cecal ligation and puncture (CLP) attenuates the tyrosine phosphorylation of insulin receptor β-subunit (IRβ) and insulin receptor substrate molecules (IRS)-1 and IRS-2.
MOLECULAR MEDICINE
(2023)
Article
Biochemistry & Molecular Biology
Gavin P. Schmitz, Manish K. Jain, Samuel T. Slocum, Bryan L. Roth
Summary: In this study, the researchers examined the effects of sequence variations in the 5-HT2AR gene on the signaling of four commonly used psychedelic drugs. They found that these genetic variations have statistically significant, but modest, effects on the efficacy and potency of the drugs. Importantly, these effects are specific to each drug.
ACS CHEMICAL NEUROSCIENCE
(2022)
Article
Biochemistry & Molecular Biology
Gavin P. Schmitz, Manish K. Jain, Samuel T. Slocum, Bryan L. Roth
Summary: Sequence variations in the 5-HT2AR gene have been found to have modest but statistically significant effects on the efficacy and potency of commonly used psychedelic drugs. The in vitro pharmacological effects of these variations are specific to each drug.
ACS CHEMICAL NEUROSCIENCE
(2022)
Article
Chemistry, Medicinal
Christian B. M. Poulie, Eline Pottie, Icaro A. Simon, Kasper Harpsoe, Laura D'Andrea, Igor V. Komarov, David E. Gloriam, Anders A. Jensen, Christophe P. Stove, Jesper L. Kristensen
Summary: This study evaluated the biased signaling of the 5-HT2AR receptor and found that the interaction with Ser159(3x36) is crucial for signaling and efficacy. G alpha(q)-mediated signaling was more affected. These findings contribute to the development of more effective 5-HT2AR agonists.
JOURNAL OF MEDICINAL CHEMISTRY
(2022)
Article
Neurosciences
Lise Guilhemsang, Amaia Gutierrez-Ceballos, Mario Antonazzo, Nicolas P. Mallet, Luisa Ugedo, Teresa Morera-Herreras
Summary: This study investigated the modulatory effects of 5-HT2A receptor stimulation on the basal ganglia circuitry, specifically targeting the mPF information processing through trans-striatal pathways. The results showed that the 5-HT2A agonist TCB-2 increased the firing rate and inhibitory response of medial SNr neurons, while the 5-HT2A receptor antagonist MDL11939 blocked these effects. Overall, these findings suggest a preferential modulatory action of 5-HT2A receptors on the dynamic regulation of basal ganglia circuitry.
JOURNAL OF NEUROSCIENCE
(2023)
Article
Biochemistry & Molecular Biology
Jean E. M. Ramirez, Ahmed B. Alarabi, Fadi T. Khasawneh, Fatima Z. Alshbool
Summary: Serotonin amplifies platelet functional responses by binding to 5HT(2A)R. However, developing antagonists for 5HT(2A)R as therapeutic agents in cardiovascular diseases has been challenging. In this study, a custom-made 5HT(2A)RAb was found to block platelet function and protect against thrombogenesis without impairing normal hemostasis.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Clinical Neurology
Gordana Nedic Erjavec, Lucija Tudor, Matea Nikolac Perkovic, Josip Podobnik, Katarina Dodig Curkovic, Mario Curkovic, Dubravka Svob Strac, Melita Cusek, Marco Bortolato, Nela Pivac
Summary: This study found an association between genetic polymorphisms of the 5-HT2A receptor and conduct disorder (CD). Certain genetic variations were strongly linked to irritability, physical aggression, and antisocial behavior. Additionally, CD subjects had significantly higher platelet 5-HT concentrations, which correlated with smoking status.
PROGRESS IN NEURO-PSYCHOPHARMACOLOGY & BIOLOGICAL PSYCHIATRY
(2022)
Article
Biochemistry & Molecular Biology
Orr Shahar, Alexander Botvinnik, Noam Esh-Zuntz, Michal Brownstien, Rachel Wolf, Amit Lotan, Gilly Wolf, Bernard Lerer, Tzuri Lifschytz
Summary: There is growing interest in the therapeutic potential of psilocybin. This study examined the role of different serotonergic receptors and TAAR1 in modulating the head twitch response induced by 5-HTP and psilocybin in mice. The findings suggest that compounds that modulate psychedelic-induced head twitch response may have important therapeutic potential.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Pharmacology & Pharmacy
Kinga Gawlinska, Dawid Gawlinski, Malgorzata Filip, Edmund Przegalinski
Summary: Recent studies have shown a relationship between maternal diet composition and the risk of mental illnesses in offspring by affecting serotonin receptors in the brain. Different maternal diets, such as high-fat, high-carbohydrate, and mixed diets, induce specific changes in 5-HT2C and 5-HT2A receptor levels in different brain regions of the offspring. Specifically, high-fat maternal diet reduces 5-HT2C receptor expression in male rats at PND 28 but increases it at PND 63 in certain brain regions.
PHARMACOLOGICAL REPORTS
(2021)
Article
Endocrinology & Metabolism
Britta Kunkemoeller, Kuangyang Chen, Sam M. Lockhart, Xuanchun Wang, Christian Rask-Madsen
Summary: Endothelial cell insulin resistance is a major contributor to diabetic complications. The study shows that CITED2 inhibits endothelial insulin signaling through the PI3K/Akt pathway by repressing HIF-dependent IRS-2 expression, and deletion of CITED2 enhances insulin signaling. Therefore, CITED2 is a novel and promising target to improve insulin sensitivity in endothelial cells and prevent vascular complications in diabetes.
AMERICAN JOURNAL OF PHYSIOLOGY-ENDOCRINOLOGY AND METABOLISM
(2021)
Article
Cell Biology
Karina A. Pena, Sofya Savransky, Breanna Lewis
Summary: Compartmentalization of GPCR signaling is an emerging topic that emphasizes the importance of spatial bias in signaling for physiological relevance. PTH1R was the first GPCR discovered to signal via cAMP from endosomes, challenging the conventional model of GPCR signaling. The location of cAMP generation determines the physiological outcomes of GPCR signaling.
MOLECULAR AND CELLULAR ENDOCRINOLOGY
(2024)
Article
Cell Biology
Cheng-Xu Ma, Xiao-Ni Ma, Jin-Jin Liu, Cong-Hui Guan, Ying-Dong Li, Nan Zhao, Didac Mauricio, Song-Bo Fu
Summary: The downregulation of primary cilia (PCs) due to BRAFV600E mutation contributes to the aggressiveness and lymph node metastasis of Papillary Thyroid Cancer (PTC).
MOLECULAR AND CELLULAR ENDOCRINOLOGY
(2024)
Article
Cell Biology
Kejun Wu, Cuihua Huang, Wenrong Zheng, Yubin Wu, Qintao Huang, Menghua Lin, Ruonan Gao, Liqin Qi, Guanlian He, Xiaoying Liu, Xiaohong Liu, Linxi Wang, Zhou Chen, Libin Liu
Summary: Recurrent non-severe hypoglycemia in patients with diabetes is associated with cognitive impairment. This study found that this condition is associated with reduced mitophagy in the hippocampus, leading to mitochondrial dysfunction and neurological impairment.
MOLECULAR AND CELLULAR ENDOCRINOLOGY
(2024)
Article
Cell Biology
Yifei Lv, Yizhou Huang, Huiyu Fan, Yunxiu Zhao, Linjuan Ma, Yibing Lan, Chunming Li, Peiqiong Chen, Zheng Lou, Jianhong Zhou
Summary: Before menopause, females have a lower incidence of cardiovascular disease than age-matched males, possibly due to the protective effects of sex hormones. 17 beta-E2 inhibits THBS1 expression, preventing cell senescence and apoptosis, and counteracts oxidative stress by suppressing the TGF-beta/Smad signaling pathway.
MOLECULAR AND CELLULAR ENDOCRINOLOGY
(2024)
Article
Cell Biology
Ana C. L. Camargo, Flavia B. Constantino, Sergio A. A. Santos, Ketlin T. Colombelli, Luiz M. F. Portela, Matheus N. Fioretto, Luisa A. Barata, Guilherme T. Valente, Carlos S. Moreno, Luis A. Justulin
Summary: This study examined the effects of maternal malnutrition on the transcriptomic landscape of the ventral prostate in rats. It found that changes in molecular pathways related to cellular development and tissue morphogenesis were associated with maternal malnutrition. The Abcg1 gene was found to be deregulated in both malnourished rats and prostate cancer models and patients.
MOLECULAR AND CELLULAR ENDOCRINOLOGY
(2024)
Article
Cell Biology
Sandra Romero-Cordoba, Mayel Chirinos, Nancy Noyola-Martinez, Nayeli Torres-Ramirez, Mitzi Garcia-Olivares, Juan Pablo Aragon-Hernandez, Ixchel Ramirez-Camacho, Rosa Zuniga, Fernando Larrea, Ali Halhali, David Barrera
Summary: This study analyzed the effects of calcitriol, TGF-131, and their combination on human trophoblast cells. The results showed that the combination treatment modified the transcriptional landscape and mainly affected the storage, activity, and metabolism of lipids, which may have an impact on placental development.
MOLECULAR AND CELLULAR ENDOCRINOLOGY
(2024)
Article
Cell Biology
Traver J. Wright, Richard B. Pyles, Melinda Sheffield-Moore, Rachel R. Deer, Kathleen M. Randolph, Kristen A. Mcgovern, Christopher P. Danesi, Charles R. Gilkison, Weston W. Ward, Jayson A. Vargas, Peyton A. Armstrong, Sarah E. Lindsay, Mohammed F. Zaidan, Justin Seashore, Tamara L. Wexler, Brent E. Masel, Randall J. Urban
Summary: This study investigates the persistent neurologic symptoms in COVID-19 patients after recovery and explores the association between these symptoms and disrupted growth hormone secretion and gastrointestinal discomfort.
MOLECULAR AND CELLULAR ENDOCRINOLOGY
(2024)
Article
Cell Biology
Li-Li Chen, Ya-Qin Li, Zhi-Hui Kang, Xuan Zhang, Su-Yan Gu, Na Wang, Xue-Yan Shen
Summary: Defects in trophoblastic EMT caused by dysregulation of circTNRC18's interaction with LIN28A play a vital role in the development of preeclampsia. LIN28A overexpression suppresses circTNRC18-mediated inhibition of trophoblast migration, invasion, and EMT, while LIN28A knockdown promotes them. Furthermore, circTNRC18 regulates the intracellular distribution of LIN28A and the expression of insulin-like growth factor II, affecting cell migration and invasion. Targeting the circTNRC18-LIN28A regulatory axis may provide a novel treatment approach for preeclampsia.
MOLECULAR AND CELLULAR ENDOCRINOLOGY
(2024)