The presenilins (PSs) are part of the molecular machinery responsible for cleaving proteins like the β-amyloid precursor protein (APP) and Notch in the plane of the membrane (Annaert and De Strooper 1999). Mutations in PS1 are one of the major causes of familiar Alzheimer's disease. PSs are also involved in regulating the Wnt/β-catenin signaling pathway, but how exactly remains a highly controversial issue (for full discussion see www.alzforum.org/members/forums/journal/catenin/index.html). In this issue, Soriano et al. 2001 provide results to tip the scales definitively in favor of the concept that PS1 operates as a negative regulator of the Wnt/β-catenin signaling pathway.
β-catenin, neural plakophilin related armadillo protein (NPRAP, also called δ-catenin), and p0071 previously were known to bind to the large cytoplasmic loop domain of PS1 (see www.alzforum.org/members/forums/journal/catenin/index.html). These proteins are all characterized by repeats of the armadillo motif,...
