Inhibitors and Modulators of β- and γ-Secretase

Most gene mutations associated with Alzheimer's disease point to the metabolism of amyloid precursor protein as potential cause. The β- and γ-secretases are two executioners of amyloid precursor protein processing resulting in amyloid β. Significant progress has been made in the selective inhibition of both proteases, regardless of structural information for γ-secretase. Several peptidic and non-peptidic leads were identified and first drug candidates are in clinical trials. This review focuses on the developments since 2003.