Article
Health Care Sciences & Services
Andrea Salmaggi, Cristina Corno, Marta Maschio, Sara Donzelli, Annachiara D'Urso, Paola Perego, Emilio Ciusani
Summary: Perampanel alone exhibits pro-apoptotic effects on glioblastoma cell lines, possibly through increased GluR2/3 expression, while a strong synergistic effect is observed when combined with temozolomide in certain cell lines. Further investigation into the impact of this combination on oncologic outcomes in glioblastoma is warranted.
JOURNAL OF PERSONALIZED MEDICINE
(2021)
Article
Biochemistry & Molecular Biology
Wenshu XiangWei, Riley E. Perszyk, Nana Liu, Yuchen Xu, Subhrajit Bhattacharya, Gil H. Shaulsky, Constance Smith-Hicks, Ali Fatemi, Andrew E. Fry, Kate Chandler, Tao Wang, Julie Vogt, Julie S. Cohen, Alex R. Paciorkowski, Annapurna Poduri, Yuehua Zhang, Shuang Wang, Yuping Wang, Qiongxiang Zhai, Fang Fang, Jie Leng, Kathryn Garber, Scott J. Myers, Robin-Tobias Jauss, Kristen L. Park, Timothy A. Benke, Johannes R. Lemke, Hongjie Yuan, Yuwu Jiang, Stephen F. Traynelis
Summary: AMPA receptors play a critical role in brain function, and mutations can affect their function and localization, possibly contributing to clinical phenotypes in patients. Evaluating receptor sensitivity to selective modulators can provide options for targeted therapeutic interventions.
CELLULAR AND MOLECULAR LIFE SCIENCES
(2023)
Review
Clinical Neurology
Fabio Perversi, Cinzia Costa, Angelo Labate, Simona Lattanzi, Claudio Liguori, Marta Maschio, Stefano Meletti, Lino Nobili, Francesca Felicia Operto, Andrea Romigi, Emilio Russo, Carlo Di Bonaventura
Summary: Glutamate is the brain's main excitatory neurotransmitter, and an imbalance of excitatory and inhibitory activities may lead to epilepsy or other neurological and psychiatric conditions. AMPA receptors, as the predominant mediator of glutamate-induced excitatory neurotransmission, are a major drug target for modulating brain functions. Perampanel (PER), a selective AMPA antagonist, has shown potential in treating various conditions beyond epilepsy. Evaluating new studies on AMPA antagonism and PER in different neurological conditions, this review aims to provide insights for future research on the use of PER and other AMPA receptor antagonists.
FRONTIERS IN NEUROLOGY
(2023)
Article
Neurosciences
Jennifer Burnsed, Weronika Matysik, Lu Yang, Huayu Sun, Suchitra Joshi, Jaideep Kapur
Summary: Postnatal maturation of the motor cortex is vital for developing motor learning capacity. During the first few weeks after birth, there are numerous neuronal and synaptic changes in the motor cortex, which vary by region and layer, likely due to different developmental functions and needs. Layer II/III of the motor cortex plays a crucial role in receiving and integrating inputs and generating attentional signals for motor learning and planning. By studying the changes in layer II/III pyramidal neurons of the mouse motor cortex from neonatal to young adult stages, we found several changes including increased dendritic branching, neuronal excitability, glutamatergic synapse number, and synaptic transmission. These changes are crucial for ongoing plasticity and motor learning capacity during development. Understanding these changes can help inform future studies on the impact of early-life injury and experiences on motor learning and development capacity.
Article
Biochemistry & Molecular Biology
Nabina Paudyal, Anindita Das, Elisa Carrillo, Vladimir Berka, Vasanthi Jayaraman
Summary: In this study, the mechanism of partial agonism in heteromeric GluK2/K5 receptors was investigated. It was found that the partial agonist AMPA-bound receptor occupied intermediate cleft closure conformational states at the GluK2 cleft, while in the full agonist glutamate-bound form, more open cleft conformations were observed. There was no significant difference in cleft closure states at the GluK5 agonist-binding domain between the partial agonist AMPA- and full agonist glutamate-bound states. Our findings suggest that partial agonism observed with AMPA binding is primarily mediated by differences in the GluK2 subunit.
PROTEINS-STRUCTURE FUNCTION AND BIOINFORMATICS
(2023)
Article
Immunology
Diego Scheggia, Jennifer Stanic, Maria Italia, Filippo La Greca, Elisa Zianni, Alberto Benussi, Barbara Borroni, Monica Di Luca, Fabrizio Gardoni
Summary: Autoantibodies targeting the GluA3 subunit of AMPARs have been found in patients with Rasmussen's encephalitis and epilepsy, and associated with learning and attention deficits. The presence of anti-GluA3 IgG in FTD patients suggests a novel pathogenic role in chronic neurodegenerative diseases. In vivo preclinical data provide insights into autoimmune encephalitis associated with anti-GluA3 IgG and indicate an additional pathological mechanism affecting excitatory synapses in FTD patients.
BRAIN BEHAVIOR AND IMMUNITY
(2021)
Review
Neurosciences
David Stroebel, Laetitia Mony, Pierre Paoletti
Summary: Ionotropic glutamate receptors (iGluRs) are essential for excitatory neurotransmission in the vertebrate CNS and play a major role in learning and memory. Some iGluR subunits do not bind glutamate, but instead bind glycine and D-serine, which have different roles and affinities in various subtypes of glycinergic iGluRs. Glycine and D-serine influence the activity and function of iGluRs, reshaping our understanding of their signaling diversity and complexity in neuropharmacology.
Article
Multidisciplinary Sciences
Mohammad Qneibi, Nidal Jaradat, Nawaf Al-Maharik, Mohammed Hawash, Linda Issa, Shorooq Suboh, Leen Yahya, Adan Abu Khait, Amjaad Warasneh, Sosana Bdir
Summary: The study investigates the composition and effects of Lavandula coronopifolia essential oil (EO) on cancer cells and AMPA receptor subunits. The EO shows high contents of eucalyptol, beta-pinene, and alpha-pinene. It demonstrates significant antiproliferative selectivity against HepG2 cancer cell lines and affects AMPA receptor kinetics. These findings suggest potential therapeutic use of Lavandula coronopifolia EO in cancer treatment and neurodegenerative diseases.
SCIENTIFIC REPORTS
(2023)
Article
Audiology & Speech-Language Pathology
Dalian Ding, Weidong Qi, Haiyan Jiang, Richard Salvi
Summary: Excessive release of glutamate at the inner hair cell-type I auditory nerve synapse leads to excitotoxicity, with potential damage extending to the spiral ganglion soma. Developmental regulation of glutamate receptors alters the pattern of excitotoxic damage, with different receptor expressions in early postnatal versus adult cochlear cultures impacting the extent of damage. AMPAR and KAR expression on specific structures closely correlates with cochlear excitotoxic damage.
Review
Cell Biology
Marina N. Vukolova, Laura Y. Yen, Margarita I. Khmyz, Alexander I. Sobolevsky, Maria V. Yelshanskaya
Summary: This review discusses the role of AMPA and kainate receptors in the pathogenesis and treatment of Parkinson's disease, epilepsy, and amyotrophic lateral sclerosis. Although these receptors represent promising therapeutic targets, their antagonists often cause adverse side effects. Further research on the factors affecting subunit expression and trafficking, as well as the regulation by novel compounds, holds promise for pharmacological studies.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2023)
Article
Biochemistry & Molecular Biology
Oleg Klykov, Shanti Pal Gangwar, Maria V. Yelshanskaya, Laura Yen, Alexander I. Sobolevsky
Summary: AMPARs mediate the majority of excitatory neurotransmission and their function is regulated by auxiliary subunits. Different types of TARP auxiliary subunits have different roles, and the structural and mechanistic variations of complexes with auxiliary subunits endow AMPARs with broad functional capabilities.
Review
Neurosciences
Lucila Perez-Gianmarco, Begum Kurt, Maria Kukley
Summary: This review focuses on the technical approaches used to study AMPARs in oligodendrocyte lineage cells and discusses future perspectives for AMPAR research in glial cells.
Article
Multidisciplinary Sciences
Maria V. Yelshanskaya, Dhilon S. Patel, Christopher M. Kottke, Maria G. Kurnikova, Alexander I. Sobolevsky
Summary: This study reveals the number of agonist binding domains required for ion channel opening and the impact of agonist binding on channel conductance in AMPA subtype ionotropic glutamate receptors. By combining structural analysis with experimental results, molecular dynamics simulations, and machine learning analysis, we found that at least two agonist binding domains are necessary for channel opening, and binding of agonist to all four domains does not guarantee maximal channel conductance.
Article
Neurosciences
Yi He, Junshi Wang, King-lun Li, Yao Q. Wang, Zachary Freyberg, Yan Dong
Summary: After drug withdrawal, incubation of drug craving progressively intensifies cue-associated drug craving. This difference provides an opportunity to determine rat-specific cellular adaptations that contribute to incubated cocaine craving in humans. Decreased membrane excitability in NAc MSNs is a prominent cellular adaptation in rats that lasts throughout prolonged drug withdrawal, while in mice, this adaptation diminishes after 45-day withdrawal. Restoring the membrane excitability of NAcSh MSNs after cocaine withdrawal decreases cocaine seeking in rats, suggesting that drug-induced membrane adaptations are essential for behavioral expression of incubated cocaine craving.
NEUROPSYCHOPHARMACOLOGY
(2023)
Review
Biochemistry & Molecular Biology
Maria Kukley
Summary: This review discusses recent experimental findings on the functional role of AMPA receptors (AMPARs) in oligodendrocyte lineage cells in vivo, in mice and in zebrafish. The studies showed that oligodendroglial AMPARs may modulate proliferation, differentiation, migration, and survival of oligodendroglial cells. Targeting AMPAR subunit composition could be an important strategy for disease treatment. However, additional research is needed to fully understand the role of AMPARs in vivo, including considering the temporal and spatial aspects of AMPAR-mediated signaling in the oligodendrocyte lineage cells.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Neurosciences
Alvin Yu, Hector Salazar, Andrew J. R. Plested, Albert Y. Lau
Article
Multidisciplinary Sciences
Mette H. Poulsen, Anahita Poshtiban, Viktoria Klippenstein, Valentina Ghisi, Andrew J. R. Plested
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2019)
Article
Biology
Benjamin Koenig, Yuchen Hao, Sophia Schwartz, Andrew J. R. Plested, Tobias Stauber
Editorial Material
Biophysics
Andrew Plested, Vasanthi Jayaraman
BIOPHYSICAL JOURNAL
(2020)
Article
Biochemistry & Molecular Biology
Iart Luca Shytaj, Bojana Lucic, Mattia Forcato, Carlotta Penzo, James Billingsley, Vibor Laketa, Steven Bosinger, Mia Stanic, Francesco Gregoretti, Laura Antonelli, Gennaro Oliva, Christian K. Frese, Aleksandra Trifunovic, Bruno Galy, Clarissa Eibl, Guido Silvestri, Silvio Bicciato, Andrea Savarino, Marina Lusic
Article
Biophysics
Hector Salazar, Sabrina Mischke, Andrew J. R. Plested
BIOPHYSICAL JOURNAL
(2020)
Editorial Material
Neurosciences
Andrew J. R. Plested
Summary: In this study, Amin et al. (2021) examined the behavior of single NMDA receptors in synaptic-like conditions to show how the unreliable coupling between agonist binding and channel opening depends on structured linkers. They found that after neurotransmitter binding, a complex molecular discussion occurs, leading to a distinction between fast synaptic events and delayed openings and failures.
Article
Multidisciplinary Sciences
Johann Biedermann, Sebastian Braunbeck, Andrew J. R. Plested, Han Sun
Summary: Fast excitatory synaptic transmission in the central nervous system relies on the AMPA-type glutamate receptor (AMPAR), which incorporates a nonselective cation channel. Recent studies combining molecular dynamic simulations and electrophysiology have revealed the ion permeation mechanisms of AMPA receptors, showing that Na+, K+, and Cs+ can permeate at physiological rates through a simple selectivity filter structure. The permissive architecture of the filter allows for rapid, nonselective cation permeation and copermeation by water, with Cs+ slightly more permeant than Na+ due to preferential binding sites.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2021)
Article
Neurosciences
Niccolo P. Pampaloni, Andrew J. R. Plested
Summary: AMPA receptors, traditionally known for their fast activation and deactivation, have been found to also exhibit slow, persistent responses through interactions with auxiliary subunits. This superactive mode is characterized by a lack of desensitization, resistance to competitive antagonists, and a prolonged current decay. These slow currents can generate accumulating responses to repetitive stimulation, potentially playing a role in short-term potentiation at excitatory synapses. Additionally, slow AMPA currents spanning cognitive time intervals in the theta rhythms have implications for neural computation and synaptic transmission in the nervous system.
JOURNAL OF PHYSIOLOGY-LONDON
(2022)
Article
Biochemistry & Molecular Biology
Sonja Minniberger, Saeid Abdolvand, Sebastian Braunbeck, Han Sun, Andrew J. R. Plested
Summary: Ionotropic glutamate receptors are ligand-gated cation channels crucial for excitatory synaptic transmission in the central nervous system. Recent cryo-EM studies have revealed open-pore structures of AMPA-type receptors, providing insights into ion selectivity. However, detailed information regarding ion occupancy and SF side-chain positioning is still lacking. Here, we incorporated partial SF sequences into the bacterial cation channel NaK and obtained high-resolution X-ray structures, revealing distinct ion occupation and structural asymmetry.
JOURNAL OF MOLECULAR BIOLOGY
(2023)
Article
Biology
Yuchen Hao, Estelle Toulme, Benjamin Koenig, Christian Rosenmund, Andrew J. R. Plested
Summary: Optical report of neurotransmitter release allows visualization of excitatory synaptic transmission. However, without targeting to synapses, the specificity of the fluorescent signal is uncertain. To address this, the reporter iGluSnFR was fused to glutamate receptor auxiliary proteins to target it to postsynaptic sites. This improved the properties of iGluSnFR and demonstrated the importance of subcellular targeting for optogenetic actuators and reporters.
Article
Biochemistry & Molecular Biology
Iva Lucic, Pin-Lian Jiang, Andreas Franz, Yuval Bursztyn, Fan Liu, Andrew J. R. Plested
Summary: Using unnatural amino acid mutagenesis, a mutant of CaMKII was created that can form a covalent linkage to Calmodulin upon UV light illumination. The binding of Calmodulin to this mutant does not perturb the oligomeric state of CaMKII, and it can be activated by UV-induced binding of Calmodulin in the absence of calcium. This mutant shows potential for controlling CaMKII activity with light.
Article
Biology
Iva Lucic, Leonie Heluin, Pin-Lian Jiang, Alejandro G. Castro Scalise, Cong Wang, Andreas Franz, Florian Heyd, Markus C. Wahl, Fan Liu, Andrew J. R. Plested
Summary: The dodecameric protein kinase CaMKII is expressed throughout the body and plays a crucial role in synaptic plasticity and memory. Contrary to previous expectations, our study reveals that subunit exchange is not the main mechanism for the spread of CaMKII activity. Instead, inter-holoenzyme phosphorylation (IHP) is identified as the mechanism for spreading phosphorylation.
Review
Physiology
Clarissa Eibl, Andrew J. R. Plested
CURRENT OPINION IN PHYSIOLOGY
(2018)