Article
Multidisciplinary Sciences
Xiaofen Liu, Weiwei Wang
Summary: This study reports the structures of the alpha 1 beta GlyR in all functional states, providing insights into the gating mechanism and functional properties of this major Cys-loop receptor. The findings reveal cooperative and symmetric structural rearrangements in the extracellular domain upon glycine binding, as well as asymmetric pore dilation in the transmembrane domain. These results explain the role of different amino acid residues in the asymmetric activation of the receptor.
NATURE COMMUNICATIONS
(2023)
Review
Biochemistry & Molecular Biology
Deepa Gautam, Ulhas P. Naik, Meghna U. Naik, Santosh K. Yadav, Rameshwar Nath Chaurasia, Debabrata Dash
Summary: This paper explores the role of platelets in neurodegenerative disorders such as Alzheimer's disease and Parkinson's disease, as well as the critical role of glutamate receptors in the pathophysiology of these diseases. By reviewing data from clinical trials, animal models, and cellular studies, it reveals the involvement of glutamate receptor dysfunction in neurodegenerative processes and provides an overview of current treatments, including glutamate receptor antagonists, for AD and PD.
Review
Neurosciences
David Ramos-Vicente, Seth G. N. Grant, Alex Bayes
Summary: Glutamate is the major excitatory neurotransmitter in both vertebrate and invertebrate nervous systems. The evolution of glutamate receptors is more complex than anticipated, with recent research proposing a new classification system for ionotropic glutamate receptors. Additionally, the evolution of animal metabotropic glutamate receptors has resulted in the formation of four classes instead of three previously recognized.
Article
Neurosciences
Mohammad Qneibi, Mohammad Hawash, Nidal Jaradat, Sosana Bdir
Summary: Background: Glutamatergic synapses mediate excitatory neurotransmission in the CNS. Objective: To investigate the modulating effect of different compounds on AMPA receptors. Methods: Patch-clamp electrophysiology was performed on HEK293T recombinant AMPAR subunits. Results: The results showed that BDZ derivatives acted as negative modulators on AMPARs, particularly BDZs (8, 9, and 15), which increased desensitization rate and delayed deactivation process. Conclusion: BDZ compounds can act as negative allosteric AMPAR modulators to restore glutamatergic synaptic transmission, with neuroprotective properties.
MOLECULAR NEUROBIOLOGY
(2022)
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)
Review
Neurosciences
Jeremy M. Henley, Jithin D. Nair, Richard Seager, Busra P. Yucel, Gavin Woodhall, Benjamin S. Henley, Karolina Talandyte, Hope I. Needs, Kevin A. Wilkinson
Summary: Epilepsy is caused by abnormal neuronal network activity. The review focuses on the role and regulation of kainate and AMPA receptors in seizure activity, discussing the impact of GluK2 and GluA2 subunits on their respective receptors' properties.
Article
Neurosciences
Amanda M. Perozzo, Patricia M. G. E. Brown, Derek Bowie
Summary: Alternative splicing and allosteric modulation by auxiliary subunits, such as TARPs, play important roles in regulating glutamatergic neurotransmission. TARP c2 is significantly affected by alternative splicing, while CNIH-3 is not. Furthermore, the effects of GSG1L and CKAMP44 on channel gating are unaffected by alternative splicing.
JOURNAL OF NEUROSCIENCE
(2023)
Review
Biochemistry & Molecular Biology
Yan Zhang, John-Man-Tak Chu, Gordon-Tin-Chun Wong
Summary: This article reviews how glutamate handling and glutamatergic function are affected by neuroinflammation and their contribution to cognitive impairment. The authors summarize the current data regarding glutamate in neurotransmission, including its receptors and regulation. They also examine the impact of inflammation on glutamate handling and neurotransmission, focusing on changes in glial cells and the effect of cytokines. Finally, they discuss the implications of these changes for perioperative neuroinflammation and perioperative neurocognitive disorders.
Article
Cell Biology
Mohammad Qneibi, Safa Nassar, Sosana Bdir, Adel Hidmi
Summary: This study explores the synthesis of new α-lipoic acid derivatives to act as potent antagonists of AMPA receptors, potentially offering a therapeutic approach for neurological diseases associated with excessive AMPA receptor activation.
Review
Neurosciences
Jonathan G. Hanley
Summary: AMPA receptors play a critical role in synaptic transmission and brain function, with their expression at synapses determining functional connectivity of neuronal circuits and underpinning learning and memory. Dysregulation of excitatory synaptic transmission and plasticity processes is involved in various neurological disorders. MiRNAs play a role in regulating AMPAR subunit expression and synaptic plasticity, potentially contributing to both physiological and pathological changes in the brain.
Article
Biochemistry & Molecular Biology
Kim Ghilarducci, Valerie C. Cabana, Camille Desroches, Kahina Chabi, Steve Bourgault, Laurent Cappadocia, Marc P. Lussier
Summary: Protein ubiquitination plays a role in various cellular functions beyond protein degradation. The study demonstrates the interaction between RNF167 and conjugating E2 enzymes, revealing submicromolar dissociation constants and providing insights into the mechanism of binding. Additionally, the research shows that GluA2 ubiquitination by UBE2N is possible only after priming by another conjugating E2 enzyme, shedding light on the ubiquitination process mediated by RNF167.
Article
Pharmacology & Pharmacy
Mohamed Z. Habib, Esraa M. Elnahas, Yasmin M. Aboul-Ela, Mai A. Ebeid, Marwa Tarek, Doaa R. Sadek, Eman A. Negm, Dina A. Abdelhakam, Sawsan Aboul-Fotouh
Summary: Several reports suggest that calcium permeable AMPA glutamate receptors with RNA hypo-editing at the GluA2 Q/R site and excitotoxicity-mediated neuronal death play a role in the pathogenesis of neurological disorders including autism spectrum disorder (ASD). This study examined the effects of risperidone treatment on Adar2 expression, GluA2 editing, oxidative/nitrosative stress, and neuronal death in a rat model of ASD. The results showed that risperidone improved behavioral deficits and increased Adar2 expression and GluA2 editing, while reducing oxidative/nitrosative stress and neurodegeneration.
EUROPEAN JOURNAL OF PHARMACOLOGY
(2023)
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
Behavioral Sciences
Russell W. Brown, Christopher G. Varnum, Liza J. Wills, Loren D. Peeters, Justin T. Gass
Summary: The study found that the positive allosteric modulator of mGlu5, CDPPB, can alleviate PPI deficits and striatal D2 signaling in the NQ model, without significant effects on locomotor activity.
PHARMACOLOGY BIOCHEMISTRY AND BEHAVIOR
(2021)
Article
Multidisciplinary Sciences
Beatriz Herguedas, Bianka K. Kohegyi, Jan-Niklas Dohrke, Jake F. Watson, Danyang Zhang, Hinze Ho, Saher A. Shaikh, Remigijus Lape, James M. Krieger, Ingo H. Greger
Summary: This study reveals how the auxiliary subunit TARP-gamma 8 modulates the gating kinetics, ion conductance, and rectification properties of AMPA receptors, providing important insights into the functional mechanism of AMPA glutamate receptors.
NATURE COMMUNICATIONS
(2022)
Review
Neurosciences
James Krieger, Ji Young Lee, Ingo H. Greger, Ivet Bahar
NEUROSCIENCE LETTERS
(2019)
Review
Biochemistry & Molecular Biology
Olivia R. Buonarati, Erik A. Hammes, Jake F. Watson, Ingo H. Greger, Johannes W. Hell
Article
Multidisciplinary Sciences
Beatriz Herguedas, Jake F. Watson, Hinze Ho, Ondrej Cais, Javier Garcia-Nafria, Ingo H. Greger
Review
Biochemistry & Molecular Biology
Jake F. Watson, Javier Garcia-Nafria
JOURNAL OF BIOLOGICAL CHEMISTRY
(2019)
Article
Biochemistry & Molecular Biology
Jan-Niklas Dohrke, Jake F. Watson, Kristian Birchall, Ingo H. Greger
JOURNAL OF BIOLOGICAL CHEMISTRY
(2020)
Article
Biochemical Research Methods
Hinze Ho, Adam Fowle, Marisa Coetzee, Ingo H. Greger, Jake F. Watson
JOURNAL OF NEUROSCIENCE METHODS
(2020)
Article
Multidisciplinary Sciences
Jake F. Watson, Alexandra Pinggera, Hinze Ho, Ingo H. Greger
Summary: Changes in AMPAR localization can regulate synaptic transmission strength. The interactions between TARP gamma 8 and AMPAR N-terminal domain are crucial for receptor accumulation and positioning at post-synapses. The study demonstrates that AMPAR C-termini only play a modulatory role, while N-terminal domain and PDZ interactions are essential for controlling transmission.
NATURE COMMUNICATIONS
(2021)
Article
Neurosciences
Peter M. Matthews, Alexandra Pinggera, Domen Kampjut, Ingo H. Greger
Summary: AMP-type glutamate receptors in the central nervous system are predominantly involved in excitatory synaptic transmission, with their signaling properties and abundance at synapses being crucial for synapse efficacy and plasticity. Unique to these receptors is the presence of interacting proteins that play a role in their complex regulation, including transient interactions with the receptor cytoplasmic tail and the N-terminal domain. Additionally, an array of transmembrane proteins act as auxiliary subunits impacting receptor trafficking, stabilization, gating, and pharmacology.