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
Luize G. Lima, Sunyoung Ham, Hyunku Shin, Edna P. Z. Chai, Erica S. H. Lek, Richard J. Lobb, Alexandra F. Muller, Suresh Mathivanan, Belinda Yeo, Yeonho Choi, Belinda S. Parker, Andreas Moller
Summary: Exosomes secreted by cancer cells play a crucial role in metastasis, with cytokines in the tumor microenvironment binding to exosomes and promoting their uptake by specific cell lineages and organs to enhance metastatic dissemination. This interaction between exosomes and cytokines is a key determinant of cancer progression.
NATURE COMMUNICATIONS
(2021)
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
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
Clinical Neurology
Giulia Braccagni, Simona Scheggi, Marco Bortolato
Summary: This study conducted a postmortem analysis of the orbitofrontal cortex in male subjects with antisocial behavior and found a significant increase in 5-HT2A receptor levels in ASB patients and a significant reduction in TPH2 levels in substance use disorder patients.
EUROPEAN ARCHIVES OF PSYCHIATRY AND CLINICAL NEUROSCIENCE
(2023)
Article
Biochemistry & Molecular Biology
Jeong-Hee Kim, Hang-Keun Kim, Young-Don Son, Jong-Hoon Kim
Summary: This study explored the relationship between 5-HT2A receptor availability and aggression traits in healthy individuals, and found significant positive correlations between 5-HT2A receptor availability and overall aggression score as well as scores on different aggression subscales in multiple brain regions.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Chemistry, Multidisciplinary
George Khelashvili, Xiaolu Cheng, Maria E. Falzone, Milka Doktorova, Alessio Accardi, Harel Weinstein
JOURNAL OF COMPUTATIONAL CHEMISTRY
(2020)
Article
Biochemistry & Molecular Biology
Beiyu Tang, Xue Li, Thorsten Maretzky, Jose Manuel Perez-Aguilar, David McIlwain, Yifang Xie, Yufang Zheng, Tak W. Mak, Harel Weinstein, Carl P. Blobel
Article
Multidisciplinary Sciences
Kamil Gotfryd, Thomas Boesen, Jonas S. Mortensen, George Khelashvili, Matthias Quick, Daniel S. Terry, Julie W. Missel, Michael V. LeVine, Pontus Gourdon, Scott C. Blanchard, Jonathan A. Javitch, Harel Weinstein, Claus J. Loland, Poul Nissen, Ulrik Gether
NATURE COMMUNICATIONS
(2020)
Meeting Abstract
Biochemistry & Molecular Biology
Alessio Accardi, Maria Falzone, Byoung-Cheol Lee, Xiaolu Cheng, George Khelashvili, Harel Weinstein
Meeting Abstract
Biochemistry & Molecular Biology
Shana Bergman, Asghar Razavi, George Khelashvili, Harel Weinstein
Article
Computer Science, Interdisciplinary Applications
Tu Mai Anh Do, Loic Pottier, Silvina Caino-Lores, Rafael Ferreira da Silva, Michel A. Cuendet, Harel Weinstein, Trilce Estrada, Michela Taufer, Ewa Deelman
Summary: Performance evaluation is crucial for understanding the behavior of scientific workflows, especially in dealing with in situ workflows. By proposing a lightweight metric, the resource usage efficiency of in situ workflow execution can be assessed, analyzing the tradeoffs of various configurable parameters and evaluating different execution scenarios.
JOURNAL OF COMPUTATIONAL SCIENCE
(2021)
Article
Biophysics
George Khelashvili, Ambrose Plante, Milka Doktorova, Harel Weinstein
Summary: Studies have shown that the fusion peptide (FP) of coronaviruses requires binding of Ca2+ ions to enhance penetration, but the mechanisms of membrane insertion and destabilization remain unclear.
BIOPHYSICAL JOURNAL
(2021)
Article
Biochemical Research Methods
Hector Carrillo-Cabada, Jeremy Benson, Asghar M. Razavi, Brianna Mulligan, Michel A. Cuendet, Harel Weinstein, Michela Taufer, Trilce Estrada
Summary: To successfully predict a protein's function, techniques that maintain its 3D information while performing at scale are necessary. Researchers extended a protein representation and neural network architecture, demonstrating applicability in protein function prediction and detection of conformational changes in protein trajectories.
IEEE-ACM TRANSACTIONS ON COMPUTATIONAL BIOLOGY AND BIOINFORMATICS
(2021)
Article
Biochemistry & Molecular Biology
Ambrose Plante, Harel Weinstein
Summary: Molecular Dynamics (MD) simulations are vital tools for ligand discovery and design, but the challenges of handling large datasets and rare events in complex molecular machines remain. A protocol called Rare Event Detection (RED) has been developed to efficiently detect functionally relevant responses to ligand binding, offering new insights into drug activity.
Article
Multidisciplinary Sciences
George R. Heath, Ekaterina Kots, Janice L. Robertson, Shifra Lansky, George Khelashvili, Harel Weinstein, Simon Scheuring
Summary: This study introduces a new technique called localization AFM (LAFM) that overcomes traditional AFM resolution limits by applying localization image reconstruction algorithms, allowing for structural analysis of biomolecules at the single-molecule level.
Meeting Abstract
Biophysics
George Khelashvili, Harel Weinstein
BIOPHYSICAL JOURNAL
(2021)
Meeting Abstract
Biophysics
Ekaterina Kots, Harel Weinstein
BIOPHYSICAL JOURNAL
(2021)
Meeting Abstract
Biophysics
Ekaterina D. Kots, Derek M. Shore, Harel Weinstein
BIOPHYSICAL JOURNAL
(2021)
Meeting Abstract
Biophysics
Ambrose Plante, Harel Weinstein
BIOPHYSICAL JOURNAL
(2021)
Meeting Abstract
Biophysics
Ekaterina D. Kots, Derek M. Shore, Harel Weinstein
BIOPHYSICAL JOURNAL
(2020)