Catalytic Site-Directed γ-Secretase Complex Inhibitors Do Not Discriminate Pharmacologically between Notch S3 and β-APP Cleavages

Abstract excerpt

The generation of gamma-secretase inhibitors which block the release of beta-amyloid peptide (Abeta) has long been an attractive therapeutic avenue for treatment or prevention of Alzheimer's disease (AD). Such inhibitors would reduce levels of Abeta available for aggregation into toxic assemblies that lead to the plaque pathology found in affected brain tissue. Cumulative evidence suggests that the S3 cleavage of...

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