Article
Biochemistry & Molecular Biology
Daniel H. Wolf, David Zheng, Christian Kohler, Bruce I. Turetsky, Kosha Ruparel, Theodore D. Satterthwaite, Mark A. Elliott, Mary E. March, Alan J. Cross, Mark A. Smith, Stephen R. Zukin, Ruben C. Gur, Raquel E. Gur
Summary: This study found individual differences in symptom reduction with the mGluR2 positive allosteric modulator AZD8529 in schizophrenia patients, as well as improved n-back fMRI activation. Despite no significant overall effects, drug versus placebo effects on brain region activation correlated with symptom reduction, suggesting broader effects across multiple symptom domains.
MOLECULAR PSYCHIATRY
(2022)
Article
Neurosciences
G. Martella, P. Bonsi, P. Imbriani, G. Sciamanna, H. Nguyen, L. Yu-Taeger, M. Schneider, S. M. Poli, R. Lutjens, A. Pisani
Summary: Impairment of long-term synaptic plasticity is a unique endophenotype of certain forms of dystonia. Broad-spectrum antimuscarinic drugs and negative allosteric modulators of metabotropic glutamate receptor subtypes may be potential therapeutic options for dystonia treatment. The findings suggest common signaling pathway dysfunction among distinct dystonia genes and indicate the potential of dipraglurant as a novel therapeutic agent for this debilitating disorder.
Editorial Material
Biochemistry & Molecular Biology
Samuel Caton, Adam Dewan
Summary: New research shows that human olfactory receptors can have stronger responses to odors through the non-competitive binding of an allosteric modulator. This modulation mechanism adds complexity to how scents are encoded in the peripheral system.
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
Biochemistry & Molecular Biology
Yongfeng Liu, Can Cao, Xi-Ping Huang, Ryan H. Gumpper, Moira M. Rachman, Sheng-Luen Shih, Brian E. Krumm, Shicheng Zhang, Brian K. Shoichet, Jonathan F. Fay, Bryan L. Roth
Summary: This study reports the high-resolution structures of MRGPRX1 receptor bound to BAM8-22 and ML382, revealing the agonist binding mode and the structural requirements for positive allosteric modulation. These findings could facilitate the structure-based design of non-opioid pain-relieving drugs.
NATURE CHEMICAL BIOLOGY
(2023)
Article
Biochemistry & Molecular Biology
Carlos Alberto Castillo, Inmaculada Ballesteros-Yanez, David Agustin Leon-Navarro, Jose Luis Albasanz, Mairena Martin
Summary: The amyloid beta peptide plays a central role in Alzheimer's disease pathology. Exposure to A beta(25-35) in rat cortical neurons increased mGluR density and affinity, along with up-regulation of adenosine A(1)R and A(2A)R. The study highlights the possible involvement of metabotropic glutamate and adenosine receptors in the early events of AD physiopathology.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
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
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
Multidisciplinary Sciences
Jonathan L. Crooke-Rosado, Sara C. Diaz-Mendez, Yamil E. Claudio-Roman, Nilsa M. Rivera, Maria A. Sosa
Summary: By utilizing bioinformatics and de novo transcriptome assembly, potential targets for specific antibodies specific to nervous system markers in freshwater prawns of the Macrobrachium spp. were identified. Antibodies were successfully developed for prawn AMPA ionotropic glutamate receptor 1, metabotropic glutamate receptor 1 and 4, and ionotropic NMDA glutamate receptor subunit 2B, aiming to expand knowledge of structural and functional mechanisms underlying prawn behavioral responses to environmental impacts.
Review
Chemistry, Medicinal
Zoltan Orgovan, Gyorgy G. Ferenczy, Gyorgy M. Keseru
Summary: Metabotropic glutamate receptors are C class G protein-coupled receptors with relevance in various psychiatric and neurological disorders, making them of considerable interest for drug development. Allosteric modulators offer advantages over orthosteric ligands, but challenges such as structure-activity relationships and pharmacological changes make optimizing them into drug candidates challenging. Subtle structural changes identified as molecular switches may modulate the functional activity of allosteric ligands in this receptor family.
Article
Reproductive Biology
Alexandra Spirkova, Veronika Kovarikova, Zuzana Sefcikova, Jozef Pisko, Martina Ksinanova, Juraj Koppel, Dusan Fabian, Stefan Cikos
Summary: The study reveals that glutamic acid can affect preimplantation embryo development through cell membrane receptors. High extracellular concentrations of glutamic acid can inhibit blastocyst development, which is of practical significance.
BIOLOGY OF REPRODUCTION
(2022)
Review
Neurosciences
Karla Frydenvang, Darryl S. Pickering, Jette Sandholm Kastrup
Summary: This paper summarizes the interaction between positive allosteric modulators (PAMs) and the ligand-binding domain (LBD) of AMPA and kainate receptors based on structure determinations. PAMs are small molecules that enhance receptor currents by interfering with receptor desensitization and are considered to be of interest for pharmacological tool development. Potent PAMs have been identified for both AMPA and kainate receptors, with potential applications in brain disorder treatment and functional investigations.
JOURNAL OF PHYSIOLOGY-LONDON
(2022)
Article
Biochemistry & Molecular Biology
Casey Trimmer, Randy Arroyave, Christine Vuilleumier, Lily Wu, Aleksey Dumer, Christie DeLaura, Jehoon Kim, Georgia M. Pierce, Maria Borisovska, Florian De Nanteuil, Matthew Emberger, Yakov Varganov, Christian Margot, Matthew E. Rogers, Patrick Pfister
Summary: Odor perception is determined by the detection of environmental volatiles at the periphery of the olfactory system. Combinatorial activation of odorant receptors allows discrimination of numerous odorants, and recent studies indicate inhibitory modulation of receptor activity in the presence of odorant mixtures. Human OR5AN1 plays a role in musk detection and certain odorants act as positive allosteric modulators, enhancing its activity in binary mixtures. This allosteric modulation of odorant receptors is perceptually relevant and adds complexity to odor coding in the peripheral olfactory system.
Article
Multidisciplinary Sciences
Marcus W. Meinhardt, Simone Pfarr, Gregory Fouquet, Cathrin Rohleder, Manuela L. Meinhardt, Janet Barroso-Flores, Rebecca Hoffmann, Jerome Jeanblanc, Elisabeth Paul, Konstantin Wagner, Anita C. Hansson, Georg Koehr, Nils Meier, Oliver von Bohlen und Halbach, Richard L. Bell, Heike Endepols, Bernd Neumaier, Kai Schoenig, Dusan Bartsch, Mickael Naassila, Rainer Spanagel, Wolfgang H. Sommer
Summary: The study identified a common molecular pathological mechanism for both executive dysfunction and alcohol craving in alcohol-dependent patients, and proposed a personalized mGluR2 mechanism-based intervention strategy for medication development.
Article
Pharmacology & Pharmacy
Vanessa Pereira, Juri Aparicio Arias, Amadeu Llebaria, Cyril Goudet
Summary: Neuropathic pain is a challenging condition to manage. In this study, the role of the amygdala in regulating neuropathic pain was investigated. The activation of mGlu4 receptors in the amygdala was found to alleviate sensory and depressive-like symptoms in a mouse model of neuropathy.
PHARMACOLOGICAL RESEARCH
(2023)