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Substrate interaction inhibits γ-secretase production of amyloid-β peptides
Combining NMR, mass spectrometry, AlphaLISA and cell assays, we discovered a compound C1 that binds C-terminal juxtamembrane lysines at the transmembrane domain of the amyloid precursor protein (APPTM) and inhibits γ-secretase production of amyloid-β with μM IC(50). Our work suggests that targeting...
| Autores principales: | , , , , , , , , , , , , , |
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| Formato: | Online Artículo Texto |
| Lenguaje: | English |
| Publicado: |
2020
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| Materias: | |
| Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8219260/ https://www.ncbi.nlm.nih.gov/pubmed/32016207 http://dx.doi.org/10.1039/c9cc09170j |
| _version_ | 1783710891984814080 |
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| author | Zhao, Jing Xiao, Yuanyuan Liu, Xinyue Kim, Soohyun Wu, Xianzhong Barros, Marilia Zhuang, Ran Hou, Xuben Zhang, Yingkai Robakis, Nikolaos K. Li, Yue-Ming Dordick, Jonathan S. Ubarretxena-Belandia, Iban Wang, Chunyu |
| author_facet | Zhao, Jing Xiao, Yuanyuan Liu, Xinyue Kim, Soohyun Wu, Xianzhong Barros, Marilia Zhuang, Ran Hou, Xuben Zhang, Yingkai Robakis, Nikolaos K. Li, Yue-Ming Dordick, Jonathan S. Ubarretxena-Belandia, Iban Wang, Chunyu |
| author_sort | Zhao, Jing |
| collection | PubMed |
| description | Combining NMR, mass spectrometry, AlphaLISA and cell assays, we discovered a compound C1 that binds C-terminal juxtamembrane lysines at the transmembrane domain of the amyloid precursor protein (APPTM) and inhibits γ-secretase production of amyloid-β with μM IC(50). Our work suggests that targeting APPTM is a novel and viable strategy in AD drug discovery. |
| format | Online Article Text |
| id | pubmed-8219260 |
| institution | National Center for Biotechnology Information |
| language | English |
| publishDate | 2020 |
| record_format | MEDLINE/PubMed |
| spelling | pubmed-82192602021-06-22 Substrate interaction inhibits γ-secretase production of amyloid-β peptides Zhao, Jing Xiao, Yuanyuan Liu, Xinyue Kim, Soohyun Wu, Xianzhong Barros, Marilia Zhuang, Ran Hou, Xuben Zhang, Yingkai Robakis, Nikolaos K. Li, Yue-Ming Dordick, Jonathan S. Ubarretxena-Belandia, Iban Wang, Chunyu Chem Commun (Camb) Article Combining NMR, mass spectrometry, AlphaLISA and cell assays, we discovered a compound C1 that binds C-terminal juxtamembrane lysines at the transmembrane domain of the amyloid precursor protein (APPTM) and inhibits γ-secretase production of amyloid-β with μM IC(50). Our work suggests that targeting APPTM is a novel and viable strategy in AD drug discovery. 2020-02-27 /pmc/articles/PMC8219260/ /pubmed/32016207 http://dx.doi.org/10.1039/c9cc09170j Text en https://creativecommons.org/licenses/by/3.0/This article is licensed under a Creative Commons Attribution-NonCommercial 3.0 Unported Licence. |
| spellingShingle | Article Zhao, Jing Xiao, Yuanyuan Liu, Xinyue Kim, Soohyun Wu, Xianzhong Barros, Marilia Zhuang, Ran Hou, Xuben Zhang, Yingkai Robakis, Nikolaos K. Li, Yue-Ming Dordick, Jonathan S. Ubarretxena-Belandia, Iban Wang, Chunyu Substrate interaction inhibits γ-secretase production of amyloid-β peptides |
| title | Substrate interaction inhibits γ-secretase production of amyloid-β peptides |
| title_full | Substrate interaction inhibits γ-secretase production of amyloid-β peptides |
| title_fullStr | Substrate interaction inhibits γ-secretase production of amyloid-β peptides |
| title_full_unstemmed | Substrate interaction inhibits γ-secretase production of amyloid-β peptides |
| title_short | Substrate interaction inhibits γ-secretase production of amyloid-β peptides |
| title_sort | substrate interaction inhibits γ-secretase production of amyloid-β peptides |
| topic | Article |
| url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8219260/ https://www.ncbi.nlm.nih.gov/pubmed/32016207 http://dx.doi.org/10.1039/c9cc09170j |
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