دورية أكاديمية
Acetylcholine receptor based chemogenetics engineered for neuronal inhibition and seizure control assessed in mice
| العنوان: | Acetylcholine receptor based chemogenetics engineered for neuronal inhibition and seizure control assessed in mice |
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| المؤلفون: | Nguyen, Quynh-Anh, Klein, Peter M., Xie, Cheng, Benthall, Katelyn N., Iafrati, Jillian, Homidan, Jesslyn, Bendor, Jacob T., Dudok, Barna, Farrell, Jordan S., Gschwind, Tilo, Porter, Charlotte L., Keravala, Annahita, Dodson, G. Steven, Soltesz, Ivan |
| المساهمون: | CODA Biotherapeutics |
| المصدر: | Nature Communications ; volume 15, issue 1 ; ISSN 2041-1723 |
| بيانات النشر: | Springer Science and Business Media LLC |
| سنة النشر: | 2024 |
| مصطلحات موضوعية: | General Physics and Astronomy, General Biochemistry, Genetics and Molecular Biology, General Chemistry, Multidisciplinary |
| الوصف: | Epilepsy is a prevalent disorder involving neuronal network hyperexcitability, yet existing therapeutic strategies often fail to provide optimal patient outcomes. Chemogenetic approaches, where exogenous receptors are expressed in defined brain areas and specifically activated by selective agonists, are appealing methods to constrain overactive neuronal activity. We developed BARNI (Bradanicline- and Acetylcholine-activated Receptor for Neuronal Inhibition), an engineered channel comprised of the α7 nicotinic acetylcholine receptor ligand-binding domain coupled to an α1 glycine receptor anion pore domain. Here we demonstrate that BARNI activation by the clinical stage α7 nicotinic acetylcholine receptor-selective agonist bradanicline effectively suppressed targeted neuronal activity, and controlled both acute and chronic seizures in male mice. Our results provide evidence for the use of an inhibitory acetylcholine-based engineered channel activatable by both exogenous and endogenous agonists as a potential therapeutic approach to treating epilepsy. |
| نوع الوثيقة: | article in journal/newspaper |
| اللغة: | English |
| DOI: | 10.1038/s41467-024-44853-8 |
| الإتاحة: | https://doi.org/10.1038/s41467-024-44853-8Test https://www.nature.com/articles/s41467-024-44853-8.pdfTest https://www.nature.com/articles/s41467-024-44853-8Test |
| حقوق: | https://creativecommons.org/licenses/by/4.0Test ; https://creativecommons.org/licenses/by/4.0Test |
| رقم الانضمام: | edsbas.8E00E485 |
| قاعدة البيانات: | BASE |
| DOI: | 10.1038/s41467-024-44853-8 |
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