Missense mutations in the genes coding for presenilin 1 and presenilin 2 cause familial Alzheimer's disease — a progressive neurodegenerative disorder of the central nervous system. Loss-of-function mutations of these genes in Drosophila, Caenorhabditis elegans and mice cause severe lethal phenotypes, which implicates the presenilins genetically in the Notch signalling pathway. The hypothesis that presenilins are aspartyl proteases that cleave the amyloid precursor protein and Notch can explain the phenotypes. Direct evidence for this hypothesis is, however, difficult to obtain. Moreover, presenilin 1 is a multifunctional protein, as exemplified by its role in the Wnt/β-catenin signalling pathway.
- Bart De Strooper
- Wim Annaert
