The physiological role of presenilins in cellular differentiation: lessonsfrom model organisms

Mutations in the human presenilin genes cause the most frequent and aggress ive forms of Alzheimer's Disease. They results in an increase of the 42 ami no acid variant of amyloid beta peptide that rapidly aggregates into neurot oxic plaques. In addition, lack of presenilin activity prevents the proteol ytic cleavage of the Notch receptor of intercellular signaling. The biologi cal role of presenilins is evolutionary conserved in animals. This review s ummarizes recent results obtained from animal models to understand presenil in activity and malfunction.