Substrate interaction inhibits γ-secretase production of amyloid-β peptides.
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ABSTRACT:
SUBMITTER: Zhao J
PROVIDER: S-EPMC8219260 | biostudies-literature | 2020 Feb
REPOSITORIES: biostudies-literature
Publications
Substrate interaction inhibits γ-secretase production of amyloid-β peptides.
Zhao Jing J Xiao Yuanyuan Y Liu Xinyue X Kim Soohyun S Wu Xianzhong X Barros Marilia M Zhuang Ran R Hou Xuben X Zhang Yingkai Y Robakis Nikolaos K NK Li Yue-Ming YM Dordick Jonathan S JS Ubarretxena-Belandia Iban I Wang Chunyu C
Chemical communications (Cambridge, England) 20200201 17
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 IC50. Our work suggests that targeting APPTM is a novel and viable strategy in AD drug discovery. ...[more]
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