Substrate interaction inhibits γ-secretase production of amyloid-β peptides.

Affiliation

Center for Biotechnology and Interdisciplinary Studies, Rensselaer Polytechnic Institute, Troy, NY 12180, USA. [Email]

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.

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