دورية أكاديمية
Downstream Allosteric Modulation of NMDA Receptors by 3-Benzazepine Derivatives
| العنوان: | Downstream Allosteric Modulation of NMDA Receptors by 3-Benzazepine Derivatives |
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| المؤلفون: | Ritter, Nadine, Disse, Paul, Aymanns, Isabel, Mücher, Lena, Schreiber, Julian A., Brenker, Christoph, Strünker, Timo, Schepmann, Dirk, Budde, Thomas, Strutz-Seebohm, Nathalie, Ametamey, Simon M., Wünsch, Bernhard, Seebohm, Guiscard |
| المصدر: | Molecular Neurobiology, 60 (12) |
| بيانات النشر: | Springer |
| سنة النشر: | 2023 |
| المجموعة: | ETH Zürich Research Collection |
| مصطلحات موضوعية: | iGluRs, GluN2B, Ifenprodil, Alternative splicing, 3-Benzazepine |
| الوصف: | N-Methyl-D-aspartate receptors (NMDARs) composed of different splice variants display distinct pH sensitivities and are crucial for learning and memory, as well as for inflammatory or injury processes. Dysregulation of the NMDAR has been linked to diseases like Parkinson's, Alzheimer's, schizophrenia, and drug addiction. The development of selective receptor modulators, therefore, constitutes a promising approach for numerous therapeutical applications. Here, we identified (R)-OF-NB1 as a promising splice variant selective NMDAR antagonist. We investigated the interaction of (R)-OF-NB1 and NMDAR from a biochemical, bioinformatical, and electrophysiological perspective to characterize the downstream allosteric modulation of NMDAR by 3-benzazepine derivatives. The allosteric modulatory pathway starts at the ifenprodil binding pocket in the amino terminal domain and immobilizes the connecting & alpha;5-helix to the ligand binding domain, resulting in inhibition. In contrast, the exon 5 splice variant GluN1-1b elevates the NMDARs flexibility and promotes the open state of its ligand binding domain. ; ISSN:0893-7648 ; ISSN:1559-1182 |
| نوع الوثيقة: | article in journal/newspaper |
| وصف الملف: | application/application/pdf |
| اللغة: | English |
| العلاقة: | info:eu-repo/semantics/altIdentifier/wos/001043360500004; http://hdl.handle.net/20.500.11850/628132Test |
| DOI: | 10.3929/ethz-b-000628132 |
| الإتاحة: | https://doi.org/20.500.11850/628132Test https://doi.org/10.3929/ethz-b-000628132Test https://doi.org/10.1007/s12035-023-03526-1Test https://hdl.handle.net/20.500.11850/628132Test |
| حقوق: | info:eu-repo/semantics/openAccess ; http://creativecommons.org/licenses/by/4.0Test/ ; Creative Commons Attribution 4.0 International |
| رقم الانضمام: | edsbas.36E7173A |
| قاعدة البيانات: | BASE |
| DOI: | 10.3929/ethz-b-000628132 |
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