γ-Secretase exosites as targets for substrate-selective lowering of Aβ generation.

Abstract excerpt

Intramembrane proteolysis by γ-secretase is critically implicated in Alzheimer disease pathogenesis by processing of its amyloid precursor protein substrate C99 into harmful amyloid-β peptide (Aβ) species. Recruitment of C99 involves binding of its N-terminal extracellular domain to exosites in γ-secretase. However, the role of these interactions has been elusive. Here, we show that the N-terminally shorter...

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