The physiological role of presenilins in cellular differentiation: lessons from model organisms

Mutations in the human presenilin genes cause the most frequent and aggressive forms of Alzheimer's Disease. They results in an increase of the 42 amino acid variant of amyloid beta peptide that rapidly aggregates into neurotoxic plaques. In addition, lack of presenilin activity prevents the proteolytic cleavage of the Notch receptor of intercellular signaling. The biological role of presenilins is evolutionary conserved in animals. This review summarizes recent results obtained from animal models to understand presenilin activity and malfunction.