Article
Behavioral Sciences
Rocio Solis-Guillen, Marcello Leopoldo, Alfredo Meneses, David Centurion
Summary: Memory is a crucial aspect of individuality, with retrieval posing a challenge for patients with memory deficits. The neurotransmitter 5-hydroxytryptamine (5-HT) is involved in memory processes, and activation of 5-HT1A and 5-HT7 receptors has been shown to enhance memory retrieval, making them potential therapeutic targets for improving long-term memory retrieval.
BEHAVIOURAL BRAIN RESEARCH
(2021)
Article
Neurosciences
Scheila Daiane Schmidt, Carolina Garrido Zinn, Lorena Evelyn Cavalcante, Flavia Fagundes Ferreira, Cristiane Regina Guerino Furini, Ivan Izquierdo, Jociane De Carvalho Myskiw
Summary: Social recognition, crucial for social group establishment, reproduction, and species survival, relies on the consolidation of social stimuli in long-term memory. This study reveals the involvement of specific serotonin receptors in the consolidation of social recognition memory, shedding light on the molecular mechanisms underlying this process.
Article
Biochemistry & Molecular Biology
Motohiro Okada, Ryusuke Matsumoto, Yoshimasa Yamamoto, Kouji Fukuyama
Summary: This study investigated the effects of lurasidone, vortioxetine, and escitalopram on 5-HT7R function and found that chronic administration of these drugs leads to downregulation of 5-HT7R in the thalamus. Furthermore, it was observed that vortioxetine and lurasidone induce more rapid downregulation of 5-HT7R through direct inhibition, while escitalopram's downregulation is slower due to its indirect elevation of extracellular serotonin levels.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Review
Neurosciences
Josephine Labus, Kian-Fritz Roehrs, Jana Ackmann, Hristo Varbanov, Franziska E. Mueller, Shaobo Jia, Kathrin Jahreis, Anna-Lena Vollbrecht, Malte Butzlaff, Yvonne Schill, Daria Guseva, Katrin Boehm, Rahul Kaushik, Monika Bijata, Philippe Marin, Severine Chaumont-Dubel, Andre Zeug, Alexander Dityatev, Evgeni Ponimaskin
Summary: Tauopathies are a group of neurodegenerative diseases characterized by the buildup of hyperphosphorylated Tau protein. This study reveals the important role of 5-HT7R/CDK5 signaling in Tauopathy, suggesting that targeting 5-HT7R could be a promising therapeutic strategy for Tauopathies. Preventing Tau hyperphosphorylation and neurotoxicity by blocking constitutive 5-HT7R activity highlights a potential treatment approach for Tau-related disorders.
PROGRESS IN NEUROBIOLOGY
(2021)
Article
Multidisciplinary Sciences
Chayma El Khamlichi, Flora Reverchon, Nadege Hervouet-Coste, Elodie Robin, Nicolas Chopin, Emmanuel Deau, Fahima Madouri, Cyril Guimpied, Cyril Colas, Arnaud Menuet, Asuka Inoue, Andrzej J. Bojarski, Gerald Guillaumet, Franck Suzenet, Eric Reiter, Severine Morisset-Lopez
Summary: This study demonstrates that Serodolin is a unique agonist/antagonist that modulates the biological functions of GPCRs through specific signaling pathways. Additionally, Serodolin has a significant analgesic effect on pain sensation and acts specifically through 5-HT7R. This research provides new insights into the molecular mechanism of 5-HT7R and the modulation of pain response.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2022)
Article
Medicine, Research & Experimental
Elias B. Nascimento Jr., R. L. Romero, Marcela M. G. B. Dutra, Bernd L. Fiebich, Igor D. G. Duarte, Marcio M. Coelho
Summary: The activation of 5-HT1D and 5-HT7 receptors plays a role in mechanical allodynia induced by 5-HT in mice, while peripheral 5-HT3 receptors have an inhibitory role in the nociceptive response induced by 5-HT or carrageenan.
BIOMEDICINE & PHARMACOTHERAPY
(2021)
Article
Chemistry, Medicinal
Edward Ofori, Edem K. Onyameh, Uma M. Gonela, Chandrashekhar Voshavar, Barbara Bricker, Tracy L. Swanson, Amy J. Eshleman, Jennifer L. Schmachtenberg, Shelley H. Bloom, Aaron J. Janowsky, Seth Y. Ablordeppey
Summary: We have conducted a study to explore the potential of dual 5-HT1AR and 5-HT7R ligands, resulting in the identification of a new compound with high affinity for these receptors. This compound, designated as 21, shows promising functional characteristics as a potential antidepressant agent.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2021)
Article
Biochemistry & Molecular Biology
Natalia Kreshchenko, Nadezhda Terenina, Artem Ermakov
Summary: This study investigates the localization of serotonin and 5-HT7 type serotonin receptors in larvae of parasitic flatworms using immunocytochemical methods and confocal laser scanning microscopy. The results indicate the presence of 5-HT7 immunoreactivity in specific structures of the worms, suggesting its importance in the motor control system of flatworms.
Article
Biochemistry & Molecular Biology
Damian Kulaga, Anna Karolina Drabczyk, Grzegorz Satala, Gniewomir Latacz, Anna Boguszewska-Czubara, Damian Plazuk, Jolanta Jaskowska
Summary: In this study, novel 1,3,5-triazine derivatives were designed and synthesized as 5-HT7 receptor ligands. Two of the tested compounds showed high affinity and moderate metabolic stability, with low hepatotoxicity.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Review
Neurosciences
Rita Bardoni
Summary: The role of 5-HT7 receptors in modulating pain perception has been explored through in vivo studies using different pain models. While most studies have reported an antinociceptive effect of 5-HT7 receptor activation, some researchers have suggested a pronociceptive action. The discrepancies in the results could be explained by differences in pain models, animal species and gender, receptor types, agonists, and route of administration. This mini-review summarizes the main findings and discusses the expression patterns, cellular mechanisms, alterations in receptor function, and the future perspectives of 5-HT7 receptors in the pain system.
CURRENT NEUROPHARMACOLOGY
(2023)
Article
Neurosciences
Antonella Comitato, Enza Lacivita, Marcello Leopoldo, Rita Bardoni
Summary: The 5-HT7 receptors play an important role in synaptic modulation, particularly in synaptic inhibition, in the dorsal horn of the spinal cord. The stronger impact on synaptic inhibition suggests that these receptors may have an anti-nociceptive role in the spinal cord of naive animals.
FRONTIERS IN MOLECULAR NEUROSCIENCE
(2022)
Review
Biochemistry & Molecular Biology
Jieon Lee, Diana Avramets, Byungsun Jeon, Hyunah Choo
Summary: Recent studies suggest that 5-HT7R could be a potential therapeutic target for the treatment of neurodevelopmental disorders by affecting neuronal morphology and modulating behavioral symptoms, offering a new approach to treating NDDs.
Article
Neurosciences
Yingtang Shi, Cleyton R. Sobrinho, Jaseph Soto-Perez, Brenda M. Milla, Daniel S. Stornetta, Ruth L. Stornetta, Ana C. Takakura, Daniel K. Mulkey, Thiago S. Moreira, Douglas A. Bayliss
Summary: Research suggests that the role of 5-HT7 receptors in RTN neurons in response to CO2 stimulation is minimal, and these receptors are not essential for respiratory activity. 5-HT7 receptors are mainly expressed in a small subset of RTN neurons, and have no impact on CO2-stimulated breathing.
JOURNAL OF PHYSIOLOGY-LONDON
(2022)
Article
Chemistry, Medicinal
Neelam Kumari, Anupriya Adhikari, Deepika Singh, Sunita Bhagat, Himanshu Ojha, Anjani K. Tiwari
Summary: Efforts are being made to improve the diagnosis and treatment of neurological disorders such as depression, anxiety, epilepsy, and schizophrenia. This study focuses on the 5-HT7 receptor and its potential for targeted therapy. The synthesis, characterization, and biological evaluation of various methoxy derivatives of 2-benzoxazolone arylpiperazine were conducted, and the C-2 substituted derivative showed high affinity for human 5-HT7 receptors.
DRUG DEVELOPMENT RESEARCH
(2022)
Article
Biochemistry & Molecular Biology
Flora Reverchon, Colleen Guillard, Lucile Mollet, Pascal Auzou, David Gosset, Fahima Madouri, Antoine Valery, Arnaud Menuet, Canan Ozsancak, Maud Pallix-Guyot, Severine Morisset-Lopez
Summary: This study reveals a dysregulation of 5-HT7 expression in natalizumab-treated multiple sclerosis (MS) patients, with an increase in 5-HT7 surface expression on T lymphocytes and CD4(+) T cell subsets. Activation of 5-HT7 receptor promotes the production of IL-10, suggesting its protective role in MS.
Editorial Material
Biochemistry & Molecular Biology
Clinton E. Canal, Marcello Leopoldo
Summary: The molecular characterization of bioactive molecules, such as small molecules targeting G-protein-coupled receptors, is becoming more complex, which affects the meanings of terms like agonist, antagonist, and selective. In the absence of detailed definitions and scientific consensus, these terms can cause confusion in the literature. We discuss this issue and offer straightforward solutions.
ACS CHEMICAL NEUROSCIENCE
(2022)
Article
Biochemistry & Molecular Biology
Eduardo Penna, Mauro Niso, Sabina Podlewska, Floriana Volpicelli, Marianna Crispino, Carla Perrone-Capano, Andrzej J. Bojarski, Enza Lacivita, Marcello Leopoldo
Summary: The kinetics of drug-target interaction has been a topic of increasing interest in the field of pharmacology. Previous studies have shown the importance of the lipophilicity of a molecule in this process, but there has been limited research on the 5-HT7 receptor (5-HT7R), a GPCR involved in neurodevelopmental and neuropsychiatric disorders. In this study, the researchers explored the structure-kinetics relationships of a specific class of ligands for the 5-HT7R and found that the position of polar groups within the molecule, rather than overall lipophilicity, influenced the interaction kinetics. Additionally, molecular docking and dynamics simulations were used to gain further insights into the relationship between structure and kinetics.
ACS CHEMICAL NEUROSCIENCE
(2022)
Article
Biochemistry & Molecular Biology
Margherita Mastromarino, Mauro Niso, Carmen Abate, Ewgenij Proschak, Mariam Dubiel, Holger Stark, Marian Castro, Enza Lacivita, Marcello Leopoldo
Summary: Long-chain arylpiperazine scaffold is a versatile template for designing CNS drugs targeting serotonin and dopamine receptors. This study synthesized and evaluated ten new arylpiperazine derivatives with affinity profiles at serotonin and dopamine receptors, aiming to treat ASD or psychosis. The new compounds incorporated antioxidant fragments to counteract oxidative stress. Compound 12a showed an affinity profile compatible with antipsychotic activity, while compound 9b had an affinity profile consistent with ASD studies. Both compounds also had antioxidant properties.
Article
Chemistry, Medicinal
Claudia Cristiano, Floriana Volpicelli, Marianna Crispino, Enza Lacivita, Roberto Russo, Marcello Leopoldo, Antonio Calignano, Carla Perrone-Capano
Summary: Autism spectrum disorders (ASD) are a group of neurodevelopmental conditions characterized by social deficits, repetitive behaviors, and altered inflammatory responses. This study found that ASD children have decreased levels of lipoxin A4 (LXA4), a mediator involved in inflammation resolution. Activation of the receptor FPR2 by a compound called MR-39 had positive effects on inflammation markers, LXA4 expression, and social behavior in validated animal models of ASD. These findings suggest that FPR2 could be a potential target for therapeutic approaches in ASD.
Article
Chemistry, Medicinal
Robert W. Garvey, Enza Lacivita, Mauro Niso, Beata Duszynska, Paul E. Harris, Marcello Leopoldo
Summary: This study reports the design, synthesis, and characterization of two novel fluorescent probes for the 5-HT1A receptor. One of the probes has the ability to selectively label the 5-HT1A receptor in pancreatic islet cells and shows useful properties for further characterization of this receptor's role.
Article
Chemistry, Medicinal
Margherita Mastromarino, Maria Favia, Igor A. Schepetkin, Lylia N. Kirpotina, Ewa Trojan, Mauro Niso, Antonio Carrieri, Monika Leskiewicz, Magdalena Regulska, Massimiliano Darida, Francesco Rossignolo, Stefano Fontana, Mark T. Quinn, Agnieszka Basta-Kaim, Marcello Leopoldo, Enza Lacivita
Summary: Formyl peptide receptor 2 (FPR2) agonists, including the newly identified ureidopropanamide derivatives, show promising potential in resolving inflammation and treating neurodegenerative disorders with underlying chronic neuroinflammation. Computational studies provide insights into the interactions between these compounds and FPR2. In vitro and in vivo experiments demonstrate the anti-inflammatory effects and improved mitochondrial function of selected compounds.
JOURNAL OF MEDICINAL CHEMISTRY
(2022)
Article
Chemistry, Multidisciplinary
Mariarita Laforgia, Loredana Amodio, Santina Colangiulo, Valentina Ungaro, Letizia Gatti, Gianpiero Lucarelli, Marcello Leopoldo, Patrizia Nardulli, Nicola A. Colabufo
Summary: Many anticancer drugs have low physicochemical stability after dilution, which can lead to delays in drug administration for cancer patients. Independent analytical studies can help reduce the public health costs caused by discarded drugs. Decitabine is more stable than previously reported.
Editorial Material
Neurosciences
Ewa Trojan, Monika Leskiewicz, Enza Lacivita, Marcello Leopoldo, Agnieszka Basta-Kaim
CURRENT NEUROPHARMACOLOGY
(2023)
Article
Biochemistry & Molecular Biology
Kinga Tylek, Ewa Trojan, Monika Leskiewicz, Fabio Francavilla, Enza Lacivita, Marcello Leopoldo, Agnieszka Basta-Kaim
Summary: A substantial body of evidence shows a link between dysfunctional acute inflammation resolution and the development of chronic inflammation. The importance of formyl peptide receptor 2 (FPR2) has been highlighted in this context. The activity of FPR2 is regulated by a range of endogenous ligands, including specialized pro-resolving mediators (SPMs) and synthetic ligands. A new potent FPR2 agonist, compound CMC23, has been found to have protective and anti-inflammatory effects.
ACS CHEMICAL NEUROSCIENCE
(2023)
Article
Cell Biology
Kinga Tylek, Ewa Trojan, Monika Leskiewicz, Imane Ghafir El Idrissi, Enza Lacivita, Marcello Leopoldo, Agnieszka Basta-Kaim
Summary: Microglial cells play a significant role in maintaining homeostasis and resolving inflammation. The study found that a new ureidopropanamide agonist, AMS21, has protective and anti-inflammatory effects in LPS-stimulated hippocampal cells. These effects are mediated through the FPR2 receptor specifically located on microglial cells.
Article
Biochemistry & Molecular Biology
Teresa Ponce-Lopez, Jose Antonio Gonzalez Alvarez Tostado, Fernando Dias, Keren Happuck Montiel Maltez
Summary: N-nitrosodiethylamine (NDEA) is a potential carcinogen that causes liver tumors, chronic inflammation, diabetes, cognitive problems, and Alzheimer's disease-like symptoms in animals. Metformin may protect against memory issues and brain inflammation triggered by NDEA.