Familial Alzheimer Disease-linked Presenilin 1 Variants Enhance Production of Both Aβ1–40 and Aβ1–42 Peptides That Are Only Partially Sensitive to a Potent Aspartyl Protease Transition State Inhibitor of “γ-Secretase”

Abstract excerpt

Presenilin 1 (PS1) plays an essential role in intramembranous "gamma-secretase" processing of several type I membrane proteins, including the beta-amyloid precursor proteins (APP) and Notch1. In this report, we examine the activity of two familial Alzheimer's disease-linked PS1 variants on the production of secreted Abeta peptides and the effects of L-685,458, a potent gamma-secretase inhibitor, on inhibition of...

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