Article
Multidisciplinary Sciences
Reuben Levy-Myers, Daniel Daudelin, Chan Hyun Na, Shanthini Sockanathan
Summary: This study demonstrates that the protein GDE3 regulates actin remodeling to release a unique subtype of extracellular vesicles (EVs) with distinct functions. GDE3 is expressed in astrocytes but not neurons and is responsible for releasing EVs containing annexin A1 and GDE3 via the protein WAVE3. Mice lacking GDE3 show decreased miniature excitatory postsynaptic current amplitudes in hippocampal neurons.
Article
Neurosciences
Adam P. Mecca, Kelly Rogers, Zachary Jacobs, Julia W. McDonald, Hannah R. Michalak, Nicole DellaGioia, Wenzhen Zhao, Ansel T. Hillmer, Nabeel Nabulsi, Keunpoong Lim, Jim Ropchan, Yiyun Huang, David Matuskey, Irina Esterlis, Richard E. Carson, Christopher H. van Dyck
Summary: Aging is associated with decreased availability of mGluR5 in the brain, primarily due to tissue loss. This reduction in mGluR5 binding may provide insight into age-related molecular changes and their relationship with brain tissue loss.
Review
Biochemistry & Molecular Biology
Shofiul Azam, Md. Jakaria, JoonSoo Kim, Jaeyong Ahn, In-Su Kim, Dong-Kug Choi
Summary: Metabotropic glutamate receptors (mGluRs), especially mGluR5, play important roles in neurodegenerative diseases and neuropsychiatric disorders. Recent research suggests that mGluR5 radioligands could be used to assess disease progression and track drug properties.
Article
Cell Biology
Jinliang Wang, Guan Yang, Xinxin Wang, Zhiyuan Wen, Lei Shuai, Jie Luo, Chong Wang, Ziruo Sun, Renqiang Liu, Jinying Ge, Xijun He, Ronghong Hua, Xijun Wang, Xiao Yang, Weiye Chen, Gongxun Zhong, Zhigao Bu
Summary: mGluR2 has been identified as an internalization factor for SARS-CoV-2, facilitating viral entry into cells. It cooperates with ACE2 to promote virus internalization through clathrin-mediated endocytosis, and its knockout in mice significantly reduces viral infection in the nasal turbinates and lungs. mGluR2 is also important for the internalization of other coronaviruses, suggesting it may be a potential target for antiviral development.
Article
Chemistry, Multidisciplinary
Ting-ting Fu, Gao Tu, Meng Ping, Guo-xun Zheng, Feng-yuan Yang, Jing-yi Yang, Yang Zhang, Xiao-jun Yao, Wei-wei Xue, Feng Zhu
Summary: This study utilized computational modeling approaches to reveal the subtype-selective mechanism of mGlu(1) and mGlu(5) receptors to different drug scaffolds, identifying critical residues that affect the binding of selective NAMs to the receptors. The results of this study can guide the rational design of novel NAMs.
ACTA PHARMACOLOGICA SINICA
(2021)
Article
Biochemistry & Molecular Biology
Katarzyna Kaczorowska, Anna Stankiewicz, Ryszard Bugno, Maria H. H. Paluchowska, Grzegorz Burnat, Piotr Branski, Paulina Cieslik, Joanna M. Wieronska, Mariusz Milik, Mateusz Nowak, Agnieszka Przybylowicz, Aneta Koziol, Agata Hogendorf, Adam S. S. Hogendorf, Justyna Kalinowska-Tluscik, Beata Duszynska, Andrzej Pilc, Andrzej J. J. Bojarski
Summary: Based on the glutamatergic theory of schizophrenia, a new compound library containing 103 members was synthesized and examined for NAM mGlu(7) activity. Active compounds were found only within the quinazolinone chemotype. The compound 2-(2-Chlorophenyl)-6-(2,3-dimethoxyphenyl)-3-methylquinazolin-4(3H)-one (A9-7, ALX-171) exhibited selective activity against other group III mGlu receptors, satisfactory drug-like properties, and showed antipsychotic-like activity in animal models.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Chemistry, Medicinal
Fabao Zhao, Unai Atxabal, Sofia Mariottini, Feng Yi, James S. Lotti, Nirvan Rouzbeh, Na Liu, Lennart Bunch, Kasper B. Hansen, Rasmus P. Clausen
Summary: The design and synthesis of (R)-3-(5-furanyl)carboxamido-2-aminopropanoic acid analogues as agonists at the glycine binding site in the GluN1 subunit of NMDA receptors were described. These novel analogues show variable potencies and agonist efficacies among different NMDA receptor subtypes, providing new opportunities for the development of therapeutic agents that can modulate specific NMDA receptor subtypes.
JOURNAL OF MEDICINAL CHEMISTRY
(2022)
Article
Biochemistry & Molecular Biology
Maryam Karimi, Alireza Mardanshahi, Hamid Irannejad, Seyed Mohammad Abedi, Sajjad Molavipordanjani
Summary: This study aimed to develop targeted radio-tracers for 5-HT7 receptors by synthesizing and labeling compounds 6 and 7. The radiolabeled compounds showed high affinity towards 5-HT7 receptors and demonstrated accumulation at the tumor site in mouse models. Inhibition of the receptors with pimozide significantly reduced tumor-to-muscle ratios.
BIOORGANIC CHEMISTRY
(2023)
Article
Chemistry, Medicinal
Monica Garcia, Virginia Llorente, Lourdes Garriga, Ute Christmann, Sergi Rodriguez-Escrich, Marina Virgili, Begona Fernandez, Magda Bordas, Eva Ayet, Javier Burgueno, Marta Pujol, Albert Dordal, Enrique Portillo-Salido, Georgia Gris, Jose Miguel Vela, Carmen Almansa
Summary: A new series of propionamide derivatives were developed as dual mu-opioid receptor agonists and sigma(1) receptor antagonists. The lead compound showed good analgesic effects in several animal models of both acute and chronic pain, with reduced gastrointestinal effects compared to oxycodone.
JOURNAL OF MEDICINAL CHEMISTRY
(2021)
Article
Chemistry, Organic
Yoshinori Tokairin, Hiroyuki Konno, Angeline Noireau, Caroline West, Hiroki Moriwaki, Vadim A. Soloshonok, Cyril Nicolas, Isabelle Gillaizeau
Summary: A new approach was developed for the asymmetric synthesis of beta-phosphorus-containing alpha-amino acids by utilizing chiral Ni(ii) complexes to catalyze the Michael addition of dehydroalanine-Schiff base with phosphine oxides and dialkyl phosphites.
ORGANIC CHEMISTRY FRONTIERS
(2021)
Article
Chemistry, Medicinal
Dexter C. Davis, Joseph D. Bungard, Sichen Chang, Alice L. Rodriguez, Annie L. Blobaum, Olivier Boutaud, Bruce J. Melancon, Colleen M. Niswender, P. Jeffrey Conn, Craig W. Lindsley
Summary: Further optimization of the VU0486321 series of highly selective and CNS-penetrant mGlu1 PAMs identified unique 'molecular switches' on the central aromatic ring that engendered positive cooperativity with multiple mGlu subtypes across the receptor family. This suggests potential therapeutic applications for mGlu1/4/7/8 PAMs and introduces the concept of a GPCR allosteric 'privileged structure'.
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS
(2021)
Article
Biochemistry & Molecular Biology
Christian B. M. Poulie, Younes Larsen, Cindie Leteneur, Gael Barthet, Walden E. Bjorn-Yoshimoto, Fanny Malhaire, Birgitte Nielsen, Jean-Phillippe Pin, Christophe Mulle, Darryl S. Pickering, Lennart Bunch
Summary: This study reports the pharmacological characterization of (S)-2-hydroxyhistidine (2a) and (S)-2-mercaptohistidine (2b) as mediators of glutamatergic neurotransmission. It was found that 2a showed no binding affinity or activity at all glutamate receptors and transporters, while 2b displayed selectivity for homomeric GluK3 receptors.
ACS CHEMICAL NEUROSCIENCE
(2022)
Article
Behavioral Sciences
Stephen W. White, Gwendolyn D. Squires, Sequioa J. Smith, Gwendolyn M. Wright, Kenneth J. Sufka, John M. Rimoldi, Rama S. Gadepalli
Summary: Research on modulation of glutamate receptors in aves under stress models shows potential clinical value in treating panic disorder and treatment-resistant depression.
PHARMACOLOGY BIOCHEMISTRY AND BEHAVIOR
(2023)
Article
Multidisciplinary Sciences
Francesca Serena Abatematteo, Pietro Delre, Ivan Mercurio, Veronica V. V. Rezelj, Dritan Siliqi, Stephanie Beaucourt, Gianluca Lattanzi, Nicola Antonio Colabufo, Marcello Leopoldo, Michele Saviano, Marco Vignuzzi, Giuseppe Felice Mangiatordi, Carmen Abate
Summary: The development of effective drugs to treat coronavirus infections is challenging. Recent evidence shows the S1R antagonist PB28 has potent antiviral activity against SARS-CoV-2, and through designing analogues, a compound with higher potency was identified. Interestingly, there is no direct correlation between S1R affinity and SARS-CoV-2 antiviral activity. Comparative docking and molecular dynamics simulations provide insights into the mechanism and lay the foundation for rational design of new S1R ligands with potent antiviral activity against SARS-CoV-2 and other viruses.
SCIENTIFIC REPORTS
(2023)
Article
Chemistry, Medicinal
Wenzhong Yan, Luyu Fan, Jing Yu, Ruiquan Liu, Huan Wang, Liang Tan, Sheng Wang, Jianjun Cheng
Summary: The novel compounds based on PCPMA scaffold were designed and synthesized, resulting in the identification of potent D2R partial agonists with good pharmacokinetic properties and unexpected selectivity against the 5-HT2A receptor. These PCPMA-derived D2R partial agonists showed suppressive effects in a mouse hyperlocomotion model, indicating their potential as novel antipsychotics.
JOURNAL OF MEDICINAL CHEMISTRY
(2021)