Article
Substance Abuse
Robert W. Peoples, Hong Ren
Summary: The study found that ethanol selectively alters individual kinetic rates involved in the gating process of NMDAR, affecting its function.
ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH
(2022)
Article
Neurosciences
Han Wang, Shiyun Lv, David Stroebel, Jinbao Zhang, Yijie Pan, Xuejing Huang, Xing Zhang, Pierre Paoletti, Shujia Zhu
Summary: NMDA receptors are important ion channels involved in synaptic transmission and plasticity. This study presents a series of cryo-EM structures of the human GluN1-GluN2A NMDA receptor, revealing the binding modes of different ligands or modulators and their effects on channel activation, inhibition, and allosteric transition.
Article
Biochemistry & Molecular Biology
Meixi He, Yi Wang, Xiaozhe Zhang, Lihua Zhang
Summary: In this study, a drug called talniflumate was successfully screened as a target for NMDARs through virtual screening. It was found to form stable interactions with GluN1-GluN2B NMDA receptors, particularly through high occupancy H-bond interactions. This approach offers an alternative choice for developing safe and efficient NMDAR inhibitors from available drugs.
JOURNAL OF BIOMOLECULAR STRUCTURE & DYNAMICS
(2022)
Article
Biochemistry & Molecular Biology
Vahide Alipour, Ramin Shabani, Farhad Rahmani-Nia, Salar Vaseghi, Mohammad Nasehi, Mohammad-Reza Zarrindast
Summary: Both Thimerosal and exercise impair social memory, but glutamatergic subunits do not play a separate and influential role in modulating memory processes.
JOURNAL OF MOLECULAR NEUROSCIENCE
(2022)
Review
Neurosciences
Simon Bossi, Lara Pizzamiglio, Pierre Paoletti
Summary: GluN3A is a subunit of the NMDA receptor family that can form glycine-activated receptors with GluN1 subunits. These excitatory glycine receptors (eGlyRs) have been discovered in specific brain regions and play a role in regulating neuronal excitability and behavior. The existence of eGlyRs expands our understanding of NMDAR diversity and glycinergic signaling, which was previously thought to be inhibitory. Given their concentration in brain regions regulating emotional responses, eGlyRs are potential therapeutic targets in neuropsychiatry.
TRENDS IN NEUROSCIENCES
(2023)
Article
Multidisciplinary Sciences
Jonathan E. Tullis, Olivia R. Buonarati, Steven J. Coultrap, Ashley M. Bourke, Erika L. Tiemeier, Matthew J. Kennedy, Paco S. Herson, K. Ulrich Bayer
Summary: The GluN2BDCaMKII mutation abolishes phosphorylation by CaMKII and DAPK1, potentially mediating neuroprotection through disruption of phosphorylation. However, S1303 phosphorylation was not increased by excitotoxic insults in hippocampal slices or global cerebral ischemia induced by cardiac arrest and cardiopulmonary resuscitation in vivo. In hippocampal cultures, S1303 phosphorylation was induced by chemical LTD but not LTP stimuli.
Article
Pharmacology & Pharmacy
Yue Zeng, Yueming Zheng, Tongtong Zhang, Fei Ye, Li Zhan, Zengwei Kou, Shujia Zhu, Zhaobing Gao
Summary: This study developed an efficient method to discover modulators of GluN3-containing NMDARs and identified WZB117 as a novel allosteric inhibitor of GluN1/GluN3 receptors.
FRONTIERS IN PHARMACOLOGY
(2022)
Review
Biochemistry & Molecular Biology
Terry A. Mcnearney, Karin N. Westlund
Summary: NMDA glutamate receptors play a crucial role in normal neuronal functions such as neuronal development, learning, and memory, but excessive activation can lead to neuronal long-term potentiation, acute pain, and excitotoxicity. The GluN1 subunit is important for ion channel formation, cellular trafficking, and nuclear localization.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Cell Biology
Xiaofang Shi, Qi Zhang, Jie Li, Xingyu Liu, Yi Zhang, Minhua Huang, Weiqing Fang, Junyu Xu, Tifei Yuan, Lin Xiao, Yi-Quan Tang, Xiao-Dong Wang, Jianhong Luo, Wei Yang
Summary: Phosphorylation levels of GluN2B-Y1070 in the mPFC are linked to depressive behaviors, blocking its phosphorylation can have antidepressant-like effects without affecting cognitive or anxiety-related behaviors in mice. Additionally, the Y1070F mutation helps increase excitatory synapse numbers, but only in the layer 5 pyramidal neurons of the mPFC.
Article
Chemistry, Medicinal
Hazem Ahmed, Livio Gisler, Nehal H. Elghazawy, Claudia Keller, Wolfgang Sippl, Steven H. Liang, Ahmed Haider, Simon M. Ametamey
Summary: GluN2B-enriched NMDARs are associated with several neurodegenerative and psychiatric diseases. In this study, a tritium-labeled form of OF-NB1 was developed as a selective GluN1/2B PET imaging agent. Competitive binding experiments and molecular simulations demonstrated the superior selectivity and performance of OF-NB1, making it a promising tool for screening potential GluN1/2B drug candidates.
Article
Physiology
Nirvan Rouzbeh, Andrew R. Rau, Avery J. Benton, Feng Yi, Carly M. Anderson, Mia R. Johns, Loren Jensen, James S. Lotti, David C. Holley, Kasper B. Hansen
Summary: NMDA-type ionotropic glutamate receptors play important roles in brain function and CNS disorders. The mechanism by which GluN1-selective competitive antagonists potentiate GluN1/3 receptors and the allosteric interactions in these receptors were explored. The study revealed that CGP-78608 and L-689,560 prevent desensitization of GluN1/3 receptors, but CGP-78608-bound receptors display higher glycine potency at GluN3 subunits. Molecular dynamics simulations suggested that the conformation of GluN1 ABD influences agonist potency at GluN3 subunits. These findings provide insights into the activation mechanism of GluN1/3 receptors and its potential implications in brain function and disease.
JOURNAL OF GENERAL PHYSIOLOGY
(2023)
Article
Biochemistry & Molecular Biology
Ravikumar Reddi, Kimberly Matulef, Erika Riederer, Pierre Moenne-Loccoz, Francis Valiyaveetil
Summary: Regulation of ion conduction through the pore of a K+ channel involves coordinated action of the activation gate and inactivation gate, with the W67F mutant of the KcsA channel showing reduced inactivation and enhanced activation rate. Structural studies provide insights into the allosteric pathway and highlight the importance of ion occupancy at the S2 site for channel inactivation.
JOURNAL OF MOLECULAR BIOLOGY
(2021)
Article
Chemistry, Multidisciplinary
Ji-yun Sun, Katsushi Kumata, Zhen Chen, Yi-ding Zhang, Jia-hui Chen, Akiko Hatori, Hua-long Fu, Jian Rong, Xiao-yun Deng, Tomoteru Yamasaki, Lin Xie, Kuan Hu, Masayuki Fujinaga, Qing-zhen Yu, Tuo Shao, Thomas Lee Collier, Lee Josephson, Yi-han Shao, Yun-fei Du, Lu Wang, Hao Xu, Ming-rong Zhang, Steven H. Liang
Summary: N-methyl-D-aspartate receptors (NMDARs) play important roles in the CNS, with GluN2B being a well-studied subtype. Two GluN2B-selective negative allosteric modulators were synthesized and preclinically evaluated for PET imaging. One PET ligand, [C-11]31, showed moderate specific binding to the GluN2B subtype.
ACTA PHARMACOLOGICA SINICA
(2021)
Article
Medicine, Research & Experimental
Xiao Liu, Marius Berthel, Grishmi Rajbhandari, Ying Zhou, Philip M. Lewis, Zhilian Yue, Gordon G. Wallace
Summary: This research developed a collagen-based hybrid tissue repair patch that can integrate into surrounding tissue and control inflammatory responses for effective post-operative inflammation control. The patch enables simultaneous loading and release of multiple drugs with controllable ratios. The demonstration of co-encapsulation and release of anti-inflammatory dexamethasone and anti-epileptic phenytoin validates the dual drug delivery ability of this versatile composite material. The material's Young's modulus was increased to 20 KPa using a biocompatible riboflavin-induced UV light cross-linking strategy. This composite material has broad potential applications and warrants further research exploration.
MOLECULAR PHARMACEUTICS
(2023)
Article
Chemistry, Physical
Yun-Chiao Yao, Zhongwu Li, Alice J. Gillen, Shari Yosinski, Mark A. Reed, Aleksandr Noy
Summary: Carbon nanotube porins demonstrate excellent biocompatibility and unique water and ion transport properties. Gating transport with external voltage increases control over ion flow and selectivity. The optimal gated CNTP device consists of a semiconducting CNTP inserted into a small membrane patch containing an internally conductive layer.
JOURNAL OF CHEMICAL PHYSICS
(2021)
Review
Neurosciences
Gary J. Iacobucci, Gabriela K. Popescu
NATURE REVIEWS NEUROSCIENCE
(2017)
Article
Neurosciences
Kirstie A. Cummings, Sophie Belin, Gabriela K. Popescu
Meeting Abstract
Biophysics
Gary J. Iacobucci, Gabriela K. Popescu
BIOPHYSICAL JOURNAL
(2018)
Meeting Abstract
Biophysics
Gary J. Iacobucci, Han Wen, Matthew Helou, Wenjun Zheng, Gabriela K. Popescu
BIOPHYSICAL JOURNAL
(2019)
Article
Biophysics
Gary J. Iacobucci, Gabriela K. Popescu
BIOPHYSICAL JOURNAL
(2020)
Article
Neurosciences
Gary J. Iacobucci, Gabriela K. Popescu
JOURNAL OF NEUROSCIENCE
(2019)
Article
Pharmacology & Pharmacy
Jamie A. Abbott, Gabriela K. Popescu
MOLECULAR PHARMACOLOGY
(2020)
News Item
Biophysics
Gabriela K. Popescu
BIOPHYSICAL JOURNAL
(2020)
Article
Multidisciplinary Sciences
Gary J. Iacobucci, Han Wen, Matthew Helou, Beiying Liu, Wenjun Zheng, Gabriela K. Popescu
Summary: NMDA receptors are excitatory channels crucial for central synapse physiology. The activation process involves a series of kinetically distinguishable, reversible steps, starting with glutamate binding and ligand-binding domain constriction, followed by transducing movement through linkers to open the gate. This study reveals a direct chemical interaction between GluN1-I642 and GluN2A-L550 as a structural change late in the activation reaction, stabilizing the receptors after opening.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2021)
Article
Neurosciences
Sophie Belin, Bruce A. Maki, James Catlin, Benjamin A. Rein, Gabriela K. Popescu
Summary: Research has found that mechanical forces can activate endogenous NMDAR currents in the central nervous system, even in the absence of synaptic glutamate release. This has important implications for understanding mechanotransduction and the physiological and pathological effects of mechanical forces on CNS cells.
JOURNAL OF NEUROSCIENCE
(2022)
Meeting Abstract
Biophysics
Hannah Premo, Beiying Liu, Gary J. Iacobucci, Gabriela K. Popescu
BIOPHYSICAL JOURNAL
(2021)
Meeting Abstract
Biophysics
Gary J. Iacobucci, Han Wen, Matthew Helou, Beiying Liu, Wenjun Zheng, Gabriela K. Popescu
BIOPHYSICAL JOURNAL
(2021)
Review
Physiology
Gary J. Iacobucci, Gabriela K. Popescu
CURRENT OPINION IN PHYSIOLOGY
(2018)
Article
Biophysics
Gary J. Iacobucci, Gabriela K. Popescu
BIOPHYSICAL JOURNAL
(2017)
Article
Biophysics
Wenjun Zheng, Han Wen, Gary J. Iacobucci, Gabriela K. Popescu
BIOPHYSICAL JOURNAL
(2017)