Substrate interaction inhibits γ-secretase production of amyloid-β peptides. Issue 17 (4th February 2020)

• Record Type: Journal Article
• Authors: 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
• Is Part Of: Chemical communications. Volume 56:Issue 17(2020)
• Page Start: 2578
• Page End: 2581
• Publication Date: 2020-02-04
• Subjects: Chemistry -- Periodicals; 540
• DOI: 10.1039/c9cc09170j
• Languages: English
• ISSNs: 1359-7345

Abstract

Abstract : A novel compound C1 interacts with C-terminal juxtamembrane lysines of amyloid precursor proteins and inhibits γ-secretase production of Aβ. Abstract : 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.