Target of γ-secretase modulators, presenilin marks the spot

Abstract
GSMs reduce the production of Aβ42 and are promising compounds for the treatment of Alzheimer disease. However, the target and mechanism of GSMs have been controversial. A study published in this issue of The EMBO Journal adds insight into this and shows that GSMs bind directly to the catalytic subunit of γ-secretase leading to altered cleavage of APP.