Characterization of NMDA receptor Allostery modulation
NMDA receptors are subject to numerous endogenous and exogenous allosteric regulations, which are essential for their complex pathophysiological functions in the brain, and serve as a basis for therapeutic targeting. However, the structural basis of many of these allosteric mechanisms remains unclea...
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| Published in | Journal of structural biology Vol. 217; no. 3; p. 108238 |
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| Main Authors | , , , , , , |
| Format | Journal Article |
| Language | English |
| Published |
United States
Elsevier Inc
01.09.2025
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| Subjects | |
| Online Access | Get full text |
| ISSN | 1047-8477 1095-8657 1095-8657 |
| DOI | 10.1016/j.jsb.2025.108238 |
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| Abstract | NMDA receptors are subject to numerous endogenous and exogenous allosteric regulations, which are essential for their complex pathophysiological functions in the brain, and serve as a basis for therapeutic targeting. However, the structural basis of many of these allosteric mechanisms remains unclear. In this study, we first utilized AlphaFold to predict the structural conformations of different NMDA receptor subtypes. Subsequent comparative analyses with experimentally resolved protein structures, coupled with validation using disulfide bond formation, revealed the high precision of these computational predictions. Based on these structures, we systematically investigated the allosteric regulation of NMDA receptors using RoseTTAFold-All-Atom. Our findings elucidated the binding sites of several allosteric modulators across different NMDA receptor subtypes and identified the key amino acids required for binding. These results reveal the structural basis of NMDA receptor allosteric regulation, providing new insights into its physiological and pathological roles, and offering potential avenues for drug development. |
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| AbstractList | NMDA receptors are subject to numerous endogenous and exogenous allosteric regulations, which are essential for their complex pathophysiological functions in the brain, and serve as a basis for therapeutic targeting. However, the structural basis of many of these allosteric mechanisms remains unclear. In this study, we first utilized AlphaFold to predict the structural conformations of different NMDA receptor subtypes. Subsequent comparative analyses with experimentally resolved protein structures, coupled with validation using disulfide bond formation, revealed the high precision of these computational predictions. Based on these structures, we systematically investigated the allosteric regulation of NMDA receptors using RoseTTAFold-All-Atom. Our findings elucidated the binding sites of several allosteric modulators across different NMDA receptor subtypes and identified the key amino acids required for binding. These results reveal the structural basis of NMDA receptor allosteric regulation, providing new insights into its physiological and pathological roles, and offering potential avenues for drug development.NMDA receptors are subject to numerous endogenous and exogenous allosteric regulations, which are essential for their complex pathophysiological functions in the brain, and serve as a basis for therapeutic targeting. However, the structural basis of many of these allosteric mechanisms remains unclear. In this study, we first utilized AlphaFold to predict the structural conformations of different NMDA receptor subtypes. Subsequent comparative analyses with experimentally resolved protein structures, coupled with validation using disulfide bond formation, revealed the high precision of these computational predictions. Based on these structures, we systematically investigated the allosteric regulation of NMDA receptors using RoseTTAFold-All-Atom. Our findings elucidated the binding sites of several allosteric modulators across different NMDA receptor subtypes and identified the key amino acids required for binding. These results reveal the structural basis of NMDA receptor allosteric regulation, providing new insights into its physiological and pathological roles, and offering potential avenues for drug development. NMDA receptors are subject to numerous endogenous and exogenous allosteric regulations, which are essential for their complex pathophysiological functions in the brain, and serve as a basis for therapeutic targeting. However, the structural basis of many of these allosteric mechanisms remains unclear. In this study, we first utilized AlphaFold to predict the structural conformations of different NMDA receptor subtypes. Subsequent comparative analyses with experimentally resolved protein structures, coupled with validation using disulfide bond formation, revealed the high precision of these computational predictions. Based on these structures, we systematically investigated the allosteric regulation of NMDA receptors using RoseTTAFold-All-Atom. Our findings elucidated the binding sites of several allosteric modulators across different NMDA receptor subtypes and identified the key amino acids required for binding. These results reveal the structural basis of NMDA receptor allosteric regulation, providing new insights into its physiological and pathological roles, and offering potential avenues for drug development. |
| ArticleNumber | 108238 |
| Author | Zhong, Rongde Liu, Yunsheng Kou, Zengwei Zhang, Jinfang Song, Wangsheng Jia, Yanyan Wu, Xianlin |
| Author_xml | – sequence: 1 givenname: Yunsheng surname: Liu fullname: Liu, Yunsheng organization: Cancer Center, Shenzhen Hospital (Futian) of Guangzhou University of Chinese Medicine, Shenzhen 518000, China – sequence: 2 givenname: Wangsheng surname: Song fullname: Song, Wangsheng organization: Jiading Branch of Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, 800 Huangjiahuayuan Road, Shanghai 201803, China – sequence: 3 givenname: Rongde surname: Zhong fullname: Zhong, Rongde organization: Department of Neurosurgery, Institute of Translational Medicine, Shenzhen Second People’s Hospital/The First Affiliated Hospital of Shenzhen University Health Science Center, Shenzhen 518035, China – sequence: 4 givenname: Jinfang surname: Zhang fullname: Zhang, Jinfang organization: Cancer Center, Shenzhen Hospital (Futian) of Guangzhou University of Chinese Medicine, Shenzhen 518000, China – sequence: 5 givenname: Xianlin surname: Wu fullname: Wu, Xianlin organization: Cancer Center, Shenzhen Hospital (Futian) of Guangzhou University of Chinese Medicine, Shenzhen 518000, China – sequence: 6 givenname: Yanyan orcidid: 0000-0001-7089-0959 surname: Jia fullname: Jia, Yanyan email: jiayanyan@fudan.edu.cn organization: ENT Institute and Otorhinolaryngology Department of Eye & ENT Hospital, State Key Laboratory of Medical Neurobiology and MOE Frontiers Center for Brain Science, Fudan University, Shanghai 200031, China – sequence: 7 givenname: Zengwei surname: Kou fullname: Kou, Zengwei email: zengwei.kou@utoronto.ca organization: Department of Laboratory Medicine and Pathobiology, Temerty Faculty of Medicine, University of Toronto, Toronto, ON M5S 1A8, Canada |
| BackLink | https://www.ncbi.nlm.nih.gov/pubmed/40819686$$D View this record in MEDLINE/PubMed |
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| Cites_doi | 10.1002/cmdc.202200484 10.1016/j.neuron.2021.05.031 10.1523/JNEUROSCI.3712-12.2013 10.1016/j.neuro.2023.12.006 10.1016/j.cell.2018.10.043 10.1073/pnas.0805624105 10.1113/JP278168 10.1002/glia.23609 10.1016/j.neuroscience.2016.08.012 10.1016/j.intimp.2022.108702 10.4103/NRR.NRR-D-24-00398 10.1016/j.neuron.2023.05.002 10.1016/j.csbj.2025.07.027 10.1016/j.cell.2018.07.028 10.1016/j.schres.2021.12.002 10.1038/s41594-023-00959-z 10.1038/nrn.2017.24 10.3389/fphys.2024.1446459 10.1038/307462a0 10.1007/s11064-025-04346-6 10.1038/nature25509 10.1038/s41586-021-03828-1 10.1080/19336950.2025.2490308 10.1074/jbc.M115.649723 10.1038/s41586-024-07487-w 10.1016/0304-3940(92)90040-E 10.1523/JNEUROSCI.0829-13.2013 10.1016/j.msard.2025.106593 10.1016/j.ijbiomac.2025.142597 10.1085/jgp.201812032 10.1126/science.adl2528 10.1016/j.bbrc.2022.01.024 10.4103/NRR.NRR-D-24-00154 10.1152/ajpcell.00353.2014 10.1016/j.cophys.2017.12.004 10.1113/JP279028 10.1016/j.celrep.2018.11.071 10.1111/cts.13623 10.3390/ijms20020309 10.1016/j.neuropharm.2021.108861 10.1002/glia.24361 10.1016/j.bbr.2023.114716 10.1038/s41586-021-03769-9 |
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| Keywords | Allostery modulation Glutamate receptor Protein prediction Protein structure AlphaFold |
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| References | Abramson (b0010) 2024; 630 eadl2528, doi:10.1126/science.adl2528 (2024). Stroebel, Casado, Paoletti (b0150) 2018; 2 Lin (b0085) 2016; 31 Zhang (b0210) 2021; 596 Lee (b0075) 2015; 308 Zhang (b0215) 2023; 30 Krishna, R. Zhang, J. B. et al. Structural Basis of the Proton Sensitivity of Human GluN1-GluN2A NMDA Receptors. Cell reports 25, 3582-3590 e3584, doi:10.1016/j.celrep.2018.11.071 (2018). Zhou (b0230) 2022; 249 Chen (b0015) 2025 Madry, Betz, Geiger, Laube (b0110) 2008; 105 Dupuis, Nicole, Groc (b0030) 2023; 111 Skowronska, K., Obara-Michlewska, M., Zielinska, M. & Albrecht, J. NMDA Receptors in Astrocytes: In Search for Roles in Neurotransmission and Astrocytic Homeostasis. Int. J. Mol. Sci. 20, doi:10.3390/ijms20020309 (2019). Wang (b0175) 2022; 594 Zheng, Kong, Wang, He, Xie (b0225) 2022; 107 Gomez-Mancilla (b0040) 2023; 16 Tahiri, Corti, Duarte (b0160) 2025; 50 Jalali-Yazdi, F., Chowdhury, S., Yoshioka, C. & Gouaux, E. Mechanisms for Zinc and Proton Inhibition of the GluN1/GluN2A NMDA Receptor. Cell 175, 1520-1532 e1515, doi:10.1016/j.cell.2018.10.043 (2018). Tovar, McGinley, Westbrook (b0165) 2013; 33 Nowak, Bregestovski, Ascher, Herbet, Prochiantz (b0115) 1984; 307 Sirrieh, MacLean, Jayaraman (b0135) 2015; 290 Saunders, A. et al. Molecular Diversity and Specializations among the Cells of the Adult Mouse Brain. Cell 174, 1015-1030 e1016, doi:10.1016/j.cell.2018.07.028 (2018). Yang (b0195) 2018; 554 Dembeck, Dieterich, Fendt (b0025) 2024; 456 Wang, H. et al. Gating mechanism and a modulatory niche of human GluN1-GluN2A NMDA receptors. Neuron 109, 2443-2456 e2445, doi:10.1016/j.neuron.2021.05.031 (2021). Liu, Jia, Kou (b0105) 2025; 16 Kou (b0060) 2019; 67 Steigerwald, R., Chou, T. H., Furukawa, H. & Wunsch, B. GluN2A-Selective NMDA Receptor Antagonists: Mimicking the U-Shaped Bioactive Conformation of TCN-201 by a [2.2]Paracyclophane System. Liu, Tang, Zhang, Li, Kou (b0100) 2025; 27 Tunyasuvunakool (b0170) 2021; 596 Xiong, Lou, Lian, Wu, Kou (b0190) 2025; 19 Yi, Bhattacharya, Thompson, Traynelis, Hansen (b0200) 2019; 597 Wu, Kou, Mo, Deng, Sun (b0185) 2016; 334 Kou (b0065) 2025; 101 Gibb (b0035) 2022; 202 Generalized biomolecular modeling and design with RoseTTAFold All-Atom. Shan, Dong, Wen, Cui, Cao (b0130) 2025; 308 e202200484, doi:10.1002/cmdc.202200484 (2022). Liu (b0090) 2024; 100 Abbott (b0005) 2024 Lei (b0080) 2023; 71 Clarke, Glasgow, Johnson (b0020) 2013; 33 Stroebel, Paoletti (b0155) 2021; 599 Liu, Shao, Lou, Kou (b0095) 2024; 15 Iacobucci, Popescu (b0050) 2017; 18 Hansen (b0045) 2018; 150 Panter, Faden (b0120) 1992; 136 Yu, Choi, Jiang, Wei (b0205) 2025; 20 Dupuis (10.1016/j.jsb.2025.108238_b0030) 2023; 111 10.1016/j.jsb.2025.108238_b0140 10.1016/j.jsb.2025.108238_b0180 Shan (10.1016/j.jsb.2025.108238_b0130) 2025; 308 Yang (10.1016/j.jsb.2025.108238_b0195) 2018; 554 Kou (10.1016/j.jsb.2025.108238_b0065) 2025; 101 10.1016/j.jsb.2025.108238_b0125 Panter (10.1016/j.jsb.2025.108238_b0120) 1992; 136 Liu (10.1016/j.jsb.2025.108238_b0090) 2024; 100 10.1016/j.jsb.2025.108238_b0220 10.1016/j.jsb.2025.108238_b0145 Zheng (10.1016/j.jsb.2025.108238_b0225) 2022; 107 Dembeck (10.1016/j.jsb.2025.108238_b0025) 2024; 456 Liu (10.1016/j.jsb.2025.108238_b0100) 2025; 27 Stroebel (10.1016/j.jsb.2025.108238_b0155) 2021; 599 Wang (10.1016/j.jsb.2025.108238_b0175) 2022; 594 Lin (10.1016/j.jsb.2025.108238_b0085) 2016; 31 Sirrieh (10.1016/j.jsb.2025.108238_b0135) 2015; 290 Tunyasuvunakool (10.1016/j.jsb.2025.108238_b0170) 2021; 596 Wu (10.1016/j.jsb.2025.108238_b0185) 2016; 334 Zhang (10.1016/j.jsb.2025.108238_b0210) 2021; 596 Nowak (10.1016/j.jsb.2025.108238_b0115) 1984; 307 Stroebel (10.1016/j.jsb.2025.108238_b0150) 2018; 2 Xiong (10.1016/j.jsb.2025.108238_b0190) 2025; 19 Hansen (10.1016/j.jsb.2025.108238_b0045) 2018; 150 Kou (10.1016/j.jsb.2025.108238_b0060) 2019; 67 Tahiri (10.1016/j.jsb.2025.108238_b0160) 2025; 50 Lee (10.1016/j.jsb.2025.108238_b0075) 2015; 308 10.1016/j.jsb.2025.108238_b0070 Chen (10.1016/j.jsb.2025.108238_b0015) 2025 Yi (10.1016/j.jsb.2025.108238_b0200) 2019; 597 Iacobucci (10.1016/j.jsb.2025.108238_b0050) 2017; 18 10.1016/j.jsb.2025.108238_b0055 Clarke (10.1016/j.jsb.2025.108238_b0020) 2013; 33 Yu (10.1016/j.jsb.2025.108238_b0205) 2025; 20 Zhou (10.1016/j.jsb.2025.108238_b0230) 2022; 249 Lei (10.1016/j.jsb.2025.108238_b0080) 2023; 71 Madry (10.1016/j.jsb.2025.108238_b0110) 2008; 105 Abbott (10.1016/j.jsb.2025.108238_b0005) 2024 Gomez-Mancilla (10.1016/j.jsb.2025.108238_b0040) 2023; 16 Gibb (10.1016/j.jsb.2025.108238_b0035) 2022; 202 Abramson (10.1016/j.jsb.2025.108238_b0010) 2024; 630 Liu (10.1016/j.jsb.2025.108238_b0095) 2024; 15 Zhang (10.1016/j.jsb.2025.108238_b0215) 2023; 30 Liu (10.1016/j.jsb.2025.108238_b0105) 2025; 16 Tovar (10.1016/j.jsb.2025.108238_b0165) 2013; 33 |
| References_xml | – volume: 33 start-page: 9150 year: 2013 end-page: 9160 ident: b0165 article-title: Triheteromeric NMDA receptors at hippocampal synapses publication-title: J. Neurosci. – reference: Zhang, J. B. et al. Structural Basis of the Proton Sensitivity of Human GluN1-GluN2A NMDA Receptors. Cell reports 25, 3582-3590 e3584, doi:10.1016/j.celrep.2018.11.071 (2018). – reference: Wang, H. et al. Gating mechanism and a modulatory niche of human GluN1-GluN2A NMDA receptors. Neuron 109, 2443-2456 e2445, doi:10.1016/j.neuron.2021.05.031 (2021). – volume: 16 start-page: 2236 year: 2023 end-page: 2252 ident: b0040 article-title: MIJ821 (onfasprodil) in healthy volunteers: First-in-human, randomized, placebo-controlled study (single ascending dose and repeated intravenous dose) publication-title: Clin. Transl. Sci. – volume: 50 start-page: 110 year: 2025 ident: b0160 article-title: Regulation of synaptic NMDA receptor activity by Post-translational modifications publication-title: Neurochem. Res. – volume: 31 start-page: 37 year: 2016 end-page: 43 ident: b0085 article-title: Regulation of oncoprotein 18/stathmin signaling by ERK concerns the resistance to taxol in nonsmall cell lung cancer cells publication-title: Cancer Biother. Radiopharm. – reference: Krishna, R. – volume: 111 start-page: 2312 year: 2023 end-page: 2328 ident: b0030 article-title: NMDA receptor functions in health and disease: Old actor, new dimensions publication-title: Neuron – volume: 107 year: 2022 ident: b0225 article-title: Spermine alleviates experimental autoimmune encephalomyelitis via regulating T cell activation and differentiation publication-title: Int. Immunopharmacol. – reference: Steigerwald, R., Chou, T. H., Furukawa, H. & Wunsch, B. GluN2A-Selective NMDA Receptor Antagonists: Mimicking the U-Shaped Bioactive Conformation of TCN-201 by a [2.2]Paracyclophane System. – volume: 16 year: 2025 ident: b0105 article-title: Bibliometric analysis of NMDA receptors: 2015–2024 publication-title: Front. Pharmacol. – volume: 249 start-page: 93 year: 2022 end-page: 97 ident: b0230 article-title: Rare presence of autoantibodies targeting to NMDA and GABA(A) receptors in schizophrenia patients publication-title: Schizophr. Res. – volume: 105 start-page: 12563 year: 2008 end-page: 12568 ident: b0110 article-title: Supralinear potentiation of NR1/NR3A excitatory glycine receptors by Zn2+ and NR1 antagonist publication-title: PNAS – volume: 596 start-page: 590 year: 2021 end-page: 596 ident: b0170 article-title: Highly accurate protein structure prediction for the human proteome publication-title: Nature – volume: 30 start-page: 629 year: 2023 end-page: 639 ident: b0215 article-title: Distinct structure and gating mechanism in diverse NMDA receptors with GluN2C and GluN2D subunits publication-title: Nat. Struct. Mol. Biol. – volume: 308 year: 2025 ident: b0130 article-title: A review of m(6)A modification in plant development and potential quality improvement publication-title: Int. J. Biol. Macromol. – volume: 597 start-page: 5495 year: 2019 end-page: 5514 ident: b0200 article-title: Functional and pharmacological properties of triheteromeric GluN1/2B/2D NMDA receptors publication-title: J. Physiol. – reference: , e202200484, doi:10.1002/cmdc.202200484 (2022). – year: 2025 ident: b0015 article-title: Davunetide promotes structural and functional recovery of the injured spinal cord by promoting autophagy publication-title: Neural Regen. Res. – reference: Jalali-Yazdi, F., Chowdhury, S., Yoshioka, C. & Gouaux, E. Mechanisms for Zinc and Proton Inhibition of the GluN1/GluN2A NMDA Receptor. Cell 175, 1520-1532 e1515, doi:10.1016/j.cell.2018.10.043 (2018). – year: 2024 ident: b0005 article-title: Allosteric inhibition of NMDA receptors by low dose ketamine publication-title: Mol. Psychiatry – volume: 596 start-page: 301 year: 2021 end-page: 305 ident: b0210 article-title: Structural basis of ketamine action on human NMDA receptors publication-title: Nature – volume: 202 year: 2022 ident: b0035 article-title: Allosteric antagonist action at triheteromeric NMDA receptors publication-title: Neuropharmacology – volume: 100 start-page: 35 year: 2024 end-page: 46 ident: b0090 article-title: Necroptosis involved in sevoflurane-induced cognitive dysfunction in aged mice by activating NMDA receptors increasing intracellular calcium publication-title: Neurotoxicology – reference: Saunders, A. et al. Molecular Diversity and Specializations among the Cells of the Adult Mouse Brain. Cell 174, 1015-1030 e1016, doi:10.1016/j.cell.2018.07.028 (2018). – volume: 15 year: 2024 ident: b0095 article-title: Structural prediction of GluN3 NMDA receptors publication-title: Front. Physiol. – volume: 18 start-page: 236 year: 2017 end-page: 249 ident: b0050 article-title: NMDA receptors: linking physiological output to biophysical operation publication-title: Nat. Rev. Neurosci. – volume: 2 start-page: 1 year: 2018 end-page: 12 ident: b0150 article-title: Triheteromeric NMDA receptors: from structure to synaptic physiology publication-title: Curr. Opin. Physiol. – volume: 67 start-page: 1344 year: 2019 end-page: 1358 ident: b0060 article-title: Vascular endothelial growth factor increases the function of calcium-impermeable AMPA receptor GluA2 subunit in astrocytes via activation of protein kinase C signaling pathway publication-title: Glia – reference: Generalized biomolecular modeling and design with RoseTTAFold All-Atom. – volume: 599 start-page: 2615 year: 2021 end-page: 2638 ident: b0155 article-title: Architecture and function of NMDA receptors: an evolutionary perspective publication-title: J. Physiol. – volume: 33 start-page: 4140 year: 2013 end-page: 4150 ident: b0020 article-title: Mechanistic and structural determinants of NMDA receptor voltage-dependent gating and slow Mg2+ unblock publication-title: J. Neurosci. – volume: 308 start-page: C570 year: 2015 end-page: C577 ident: b0075 article-title: A neuroprotective role of the NMDA receptor subunit GluN3A (NR3A) in ischemic stroke of the adult mouse publication-title: Am. J. Physiol. Cell Physiol. – reference: , eadl2528, doi:10.1126/science.adl2528 (2024). – volume: 71 start-page: 1648 year: 2023 end-page: 1666 ident: b0080 article-title: Vascular endothelial growth factor promotes transdifferentiation of astrocytes into neurons via activation of the MAPK/Erk-Pax6 signal pathway publication-title: Glia – volume: 27 start-page: 3167 year: 2025 end-page: 3180 ident: b0100 article-title: Artificial intelligence insight on structural basis and small molecule binding niches of NMDA receptor publication-title: Comput. Struct. Biotechnol. J. – volume: 290 start-page: 12812 year: 2015 end-page: 12820 ident: b0135 article-title: Subtype-dependent N-methyl-D-aspartate receptor amino-terminal domain conformations and modulation by spermine publication-title: J. Biol. Chem. – volume: 456 year: 2024 ident: b0025 article-title: The GluN2C/D-specific positive allosteric modulator CIQ rescues delay-induced working memory deficits in mice publication-title: Behav. Brain Res. – volume: 19 year: 2025 ident: b0190 article-title: The GluN3-containing NMDA receptors publication-title: Channels – reference: Skowronska, K., Obara-Michlewska, M., Zielinska, M. & Albrecht, J. NMDA Receptors in Astrocytes: In Search for Roles in Neurotransmission and Astrocytic Homeostasis. Int. J. Mol. Sci. 20, doi:10.3390/ijms20020309 (2019). – volume: 307 start-page: 462 year: 1984 end-page: 465 ident: b0115 article-title: Magnesium gates glutamate-activated channels in mouse central neurones publication-title: Nature – volume: 334 start-page: 275 year: 2016 end-page: 282 ident: b0185 article-title: Neurovascular coupling protects neurons against hypoxic injury via inhibition of potassium currents by generation of nitric oxide in direct neuron and endothelium cocultures publication-title: Neuroscience – volume: 20 start-page: 1981 year: 2025 end-page: 1988 ident: b0205 article-title: Acute and chronic excitotoxicity in ischemic stroke and late-onset Alzheimer's disease publication-title: Neural Regen. Res. – volume: 150 start-page: 1081 year: 2018 end-page: 1105 ident: b0045 article-title: Structure, function, and allosteric modulation of NMDA receptors publication-title: J. Gen. Physiol. – volume: 101 year: 2025 ident: b0065 article-title: Comment on the use of AI-based protein design for autoimmune encephalitis: exciting possibilities and practical considerations publication-title: Mult. Scler. Relat. Disord. – volume: 594 start-page: 46 year: 2022 end-page: 56 ident: b0175 article-title: Glutamatergic receptor and neuroplasticity in depression: Implications for ketamine and rapastinel as the rapid-acting antidepressants publication-title: Biochem. Biophys. Res. Commun. – volume: 630 start-page: 493 year: 2024 end-page: 500 ident: b0010 article-title: Accurate structure prediction of biomolecular interactions with AlphaFold 3 publication-title: Nature – volume: 136 start-page: 165 year: 1992 end-page: 168 ident: b0120 article-title: Pretreatment with NMDA antagonists limits release of excitatory amino acids following traumatic brain injury publication-title: Neurosci. Lett. – volume: 554 start-page: 317 year: 2018 end-page: 322 ident: b0195 article-title: Ketamine blocks bursting in the lateral habenula to rapidly relieve depression publication-title: Nature – ident: 10.1016/j.jsb.2025.108238_b0145 doi: 10.1002/cmdc.202200484 – ident: 10.1016/j.jsb.2025.108238_b0180 doi: 10.1016/j.neuron.2021.05.031 – volume: 33 start-page: 4140 year: 2013 ident: 10.1016/j.jsb.2025.108238_b0020 article-title: Mechanistic and structural determinants of NMDA receptor voltage-dependent gating and slow Mg2+ unblock publication-title: J. Neurosci. doi: 10.1523/JNEUROSCI.3712-12.2013 – volume: 100 start-page: 35 year: 2024 ident: 10.1016/j.jsb.2025.108238_b0090 article-title: Necroptosis involved in sevoflurane-induced cognitive dysfunction in aged mice by activating NMDA receptors increasing intracellular calcium publication-title: Neurotoxicology doi: 10.1016/j.neuro.2023.12.006 – ident: 10.1016/j.jsb.2025.108238_b0055 doi: 10.1016/j.cell.2018.10.043 – volume: 105 start-page: 12563 year: 2008 ident: 10.1016/j.jsb.2025.108238_b0110 article-title: Supralinear potentiation of NR1/NR3A excitatory glycine receptors by Zn2+ and NR1 antagonist publication-title: PNAS doi: 10.1073/pnas.0805624105 – volume: 597 start-page: 5495 year: 2019 ident: 10.1016/j.jsb.2025.108238_b0200 article-title: Functional and pharmacological properties of triheteromeric GluN1/2B/2D NMDA receptors publication-title: J. Physiol. doi: 10.1113/JP278168 – volume: 67 start-page: 1344 year: 2019 ident: 10.1016/j.jsb.2025.108238_b0060 article-title: Vascular endothelial growth factor increases the function of calcium-impermeable AMPA receptor GluA2 subunit in astrocytes via activation of protein kinase C signaling pathway publication-title: Glia doi: 10.1002/glia.23609 – volume: 334 start-page: 275 year: 2016 ident: 10.1016/j.jsb.2025.108238_b0185 article-title: Neurovascular coupling protects neurons against hypoxic injury via inhibition of potassium currents by generation of nitric oxide in direct neuron and endothelium cocultures publication-title: Neuroscience doi: 10.1016/j.neuroscience.2016.08.012 – volume: 107 year: 2022 ident: 10.1016/j.jsb.2025.108238_b0225 article-title: Spermine alleviates experimental autoimmune encephalomyelitis via regulating T cell activation and differentiation publication-title: Int. Immunopharmacol. doi: 10.1016/j.intimp.2022.108702 – volume: 16 year: 2025 ident: 10.1016/j.jsb.2025.108238_b0105 article-title: Bibliometric analysis of NMDA receptors: 2015–2024 publication-title: Front. Pharmacol. – volume: 20 start-page: 1981 year: 2025 ident: 10.1016/j.jsb.2025.108238_b0205 article-title: Acute and chronic excitotoxicity in ischemic stroke and late-onset Alzheimer's disease publication-title: Neural Regen. Res. doi: 10.4103/NRR.NRR-D-24-00398 – year: 2024 ident: 10.1016/j.jsb.2025.108238_b0005 article-title: Allosteric inhibition of NMDA receptors by low dose ketamine publication-title: Mol. Psychiatry – volume: 111 start-page: 2312 year: 2023 ident: 10.1016/j.jsb.2025.108238_b0030 article-title: NMDA receptor functions in health and disease: Old actor, new dimensions publication-title: Neuron doi: 10.1016/j.neuron.2023.05.002 – volume: 27 start-page: 3167 year: 2025 ident: 10.1016/j.jsb.2025.108238_b0100 article-title: Artificial intelligence insight on structural basis and small molecule binding niches of NMDA receptor publication-title: Comput. Struct. Biotechnol. J. doi: 10.1016/j.csbj.2025.07.027 – ident: 10.1016/j.jsb.2025.108238_b0125 doi: 10.1016/j.cell.2018.07.028 – volume: 249 start-page: 93 year: 2022 ident: 10.1016/j.jsb.2025.108238_b0230 article-title: Rare presence of autoantibodies targeting to NMDA and GABA(A) receptors in schizophrenia patients publication-title: Schizophr. Res. doi: 10.1016/j.schres.2021.12.002 – volume: 30 start-page: 629 year: 2023 ident: 10.1016/j.jsb.2025.108238_b0215 article-title: Distinct structure and gating mechanism in diverse NMDA receptors with GluN2C and GluN2D subunits publication-title: Nat. Struct. Mol. Biol. doi: 10.1038/s41594-023-00959-z – volume: 18 start-page: 236 year: 2017 ident: 10.1016/j.jsb.2025.108238_b0050 article-title: NMDA receptors: linking physiological output to biophysical operation publication-title: Nat. Rev. Neurosci. doi: 10.1038/nrn.2017.24 – volume: 15 year: 2024 ident: 10.1016/j.jsb.2025.108238_b0095 article-title: Structural prediction of GluN3 NMDA receptors publication-title: Front. Physiol. doi: 10.3389/fphys.2024.1446459 – volume: 307 start-page: 462 year: 1984 ident: 10.1016/j.jsb.2025.108238_b0115 article-title: Magnesium gates glutamate-activated channels in mouse central neurones publication-title: Nature doi: 10.1038/307462a0 – volume: 50 start-page: 110 year: 2025 ident: 10.1016/j.jsb.2025.108238_b0160 article-title: Regulation of synaptic NMDA receptor activity by Post-translational modifications publication-title: Neurochem. Res. doi: 10.1007/s11064-025-04346-6 – volume: 554 start-page: 317 year: 2018 ident: 10.1016/j.jsb.2025.108238_b0195 article-title: Ketamine blocks bursting in the lateral habenula to rapidly relieve depression publication-title: Nature doi: 10.1038/nature25509 – volume: 596 start-page: 590 year: 2021 ident: 10.1016/j.jsb.2025.108238_b0170 article-title: Highly accurate protein structure prediction for the human proteome publication-title: Nature doi: 10.1038/s41586-021-03828-1 – volume: 19 year: 2025 ident: 10.1016/j.jsb.2025.108238_b0190 article-title: The GluN3-containing NMDA receptors publication-title: Channels doi: 10.1080/19336950.2025.2490308 – volume: 290 start-page: 12812 year: 2015 ident: 10.1016/j.jsb.2025.108238_b0135 article-title: Subtype-dependent N-methyl-D-aspartate receptor amino-terminal domain conformations and modulation by spermine publication-title: J. Biol. Chem. doi: 10.1074/jbc.M115.649723 – volume: 630 start-page: 493 year: 2024 ident: 10.1016/j.jsb.2025.108238_b0010 article-title: Accurate structure prediction of biomolecular interactions with AlphaFold 3 publication-title: Nature doi: 10.1038/s41586-024-07487-w – volume: 136 start-page: 165 year: 1992 ident: 10.1016/j.jsb.2025.108238_b0120 article-title: Pretreatment with NMDA antagonists limits release of excitatory amino acids following traumatic brain injury publication-title: Neurosci. Lett. doi: 10.1016/0304-3940(92)90040-E – volume: 33 start-page: 9150 year: 2013 ident: 10.1016/j.jsb.2025.108238_b0165 article-title: Triheteromeric NMDA receptors at hippocampal synapses publication-title: J. Neurosci. doi: 10.1523/JNEUROSCI.0829-13.2013 – volume: 101 year: 2025 ident: 10.1016/j.jsb.2025.108238_b0065 article-title: Comment on the use of AI-based protein design for autoimmune encephalitis: exciting possibilities and practical considerations publication-title: Mult. Scler. Relat. Disord. doi: 10.1016/j.msard.2025.106593 – volume: 308 year: 2025 ident: 10.1016/j.jsb.2025.108238_b0130 article-title: A review of m(6)A modification in plant development and potential quality improvement publication-title: Int. J. Biol. Macromol. doi: 10.1016/j.ijbiomac.2025.142597 – volume: 150 start-page: 1081 year: 2018 ident: 10.1016/j.jsb.2025.108238_b0045 article-title: Structure, function, and allosteric modulation of NMDA receptors publication-title: J. Gen. Physiol. doi: 10.1085/jgp.201812032 – ident: 10.1016/j.jsb.2025.108238_b0070 doi: 10.1126/science.adl2528 – volume: 594 start-page: 46 year: 2022 ident: 10.1016/j.jsb.2025.108238_b0175 article-title: Glutamatergic receptor and neuroplasticity in depression: Implications for ketamine and rapastinel as the rapid-acting antidepressants publication-title: Biochem. Biophys. Res. Commun. doi: 10.1016/j.bbrc.2022.01.024 – year: 2025 ident: 10.1016/j.jsb.2025.108238_b0015 article-title: Davunetide promotes structural and functional recovery of the injured spinal cord by promoting autophagy publication-title: Neural Regen. Res. doi: 10.4103/NRR.NRR-D-24-00154 – volume: 308 start-page: C570 year: 2015 ident: 10.1016/j.jsb.2025.108238_b0075 article-title: A neuroprotective role of the NMDA receptor subunit GluN3A (NR3A) in ischemic stroke of the adult mouse publication-title: Am. J. Physiol. Cell Physiol. doi: 10.1152/ajpcell.00353.2014 – volume: 31 start-page: 37 year: 2016 ident: 10.1016/j.jsb.2025.108238_b0085 article-title: Regulation of oncoprotein 18/stathmin signaling by ERK concerns the resistance to taxol in nonsmall cell lung cancer cells publication-title: Cancer Biother. Radiopharm. – volume: 2 start-page: 1 year: 2018 ident: 10.1016/j.jsb.2025.108238_b0150 article-title: Triheteromeric NMDA receptors: from structure to synaptic physiology publication-title: Curr. Opin. Physiol. doi: 10.1016/j.cophys.2017.12.004 – volume: 599 start-page: 2615 year: 2021 ident: 10.1016/j.jsb.2025.108238_b0155 article-title: Architecture and function of NMDA receptors: an evolutionary perspective publication-title: J. Physiol. doi: 10.1113/JP279028 – ident: 10.1016/j.jsb.2025.108238_b0220 doi: 10.1016/j.celrep.2018.11.071 – volume: 16 start-page: 2236 year: 2023 ident: 10.1016/j.jsb.2025.108238_b0040 article-title: MIJ821 (onfasprodil) in healthy volunteers: First-in-human, randomized, placebo-controlled study (single ascending dose and repeated intravenous dose) publication-title: Clin. Transl. Sci. doi: 10.1111/cts.13623 – ident: 10.1016/j.jsb.2025.108238_b0140 doi: 10.3390/ijms20020309 – volume: 202 year: 2022 ident: 10.1016/j.jsb.2025.108238_b0035 article-title: Allosteric antagonist action at triheteromeric NMDA receptors publication-title: Neuropharmacology doi: 10.1016/j.neuropharm.2021.108861 – volume: 71 start-page: 1648 year: 2023 ident: 10.1016/j.jsb.2025.108238_b0080 article-title: Vascular endothelial growth factor promotes transdifferentiation of astrocytes into neurons via activation of the MAPK/Erk-Pax6 signal pathway publication-title: Glia doi: 10.1002/glia.24361 – volume: 456 year: 2024 ident: 10.1016/j.jsb.2025.108238_b0025 article-title: The GluN2C/D-specific positive allosteric modulator CIQ rescues delay-induced working memory deficits in mice publication-title: Behav. Brain Res. doi: 10.1016/j.bbr.2023.114716 – volume: 596 start-page: 301 year: 2021 ident: 10.1016/j.jsb.2025.108238_b0210 article-title: Structural basis of ketamine action on human NMDA receptors publication-title: Nature doi: 10.1038/s41586-021-03769-9 |
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