Important functional role of residue x of the presenilin GxGD protease active site motif for APP substrate cleavage specificity and substrate selectivity of γ-secretase.

Abstract excerpt

γ-Secretase plays a central role in the generation of the Alzheimer disease-causing amyloid β-peptide (Aβ) from the β-amyloid precursor protein (APP) and is thus a major Alzheimer's disease drug target. As several other γ-secretase substrates including Notch1 and CD44 have crucial signaling functions, an understanding of the mechanism of substrate recognition and cleavage is key for the development of APP...

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