Abstract
Genetic and biological studies provide evidence that the deposition of amyloid-β peptide contributes to the etiology of Alzheimer's disease (AD). Amyloid-β peptides are generated from amyloid-β precursor protein by β- and γ-secretases that are plausible molecular targets for AD treatment. γ-Secretase is an intramembrane-cleaving aspartic protease that is composed of a membrane protein complex containing presenilin. This patent describes a method to inhibit γ-secretase-mediated cleavage by new cell-permeable peptides that are designed on the basis of the interaction mode of amyloid-β precursor protein and presenilin. This patent provides a new strategy for the modulation of the γ-secretase activity towards the development of AD therapeutics.