Substrate interaction inhibits -secretase production of amyloid- peptides
CHEMICAL COMMUNICATIONS(2020)
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 gamma-secretase production of amyloid-beta with mu M IC50. Our work suggests that targeting APPTM is a novel and viable strategy in AD drug discovery.
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