Michael S. Wolfe

This study shows that AHA1 regulates Aβ production by modulating APP expression and γ-secretase assembly, suggesting it as a therapeutic target for Alzheimer's disease.

This study identifies initial cleavage sites of γ-secretase substrates NRG1 and CDH1 and confirms the phenylalanine rule at the P2 position.

This study shows that phenylalanine residues in the Notch1 transmembrane domain affect γ-secretase cleavage efficiency and site specificity, similar to the known rule for APP.

This study shows that FAD mutations in PSEN1 and APP cause stalled γ-secretase complexes, leading to synaptic degeneration, and that the F386S mutation specifically affects Aβ trimming without impairing endoproteolysis.

This study uses molecular dynamics simulations and mass spectrometry to model how γ-secretase cleaves Notch1, revealing structural dynamics and substrate interactions.

This study shows that Alzheimer's mutations stabilize harmful enzyme-substrate complexes in gamma-secretase, leading to synaptic loss rather than the released Aβ peptides being the primary cause.