Presenilin structure, function and role in Alzheimer disease

Numerous missense mutations in the presenilins are associated with the auto somal dominant form of familial Alzheimer disease. Presenilin genes encode polytopic transmembrane proteins, which are processed by proteolytic cleava ge and form high-molecular-weight complexes under physiological conditions. The presenilins have been suggested to be functionally involved in develop mental morphogenesis, unfolded protein responses and processing of selected proteins including the beta-amyloid precursor protein. Although the underl ying mechanism by which presenilin mutations lead to development of Alzheim er disease remains elusive, one consistent mutational effect is an overprod uction of long-tailed amyloid beta-peptides. Furthermore, presenilins inter act with beta-catenin to form presenilin complexes, and the physiological a nd mutational effects are also observed in the catenin signal transduction pathway. (C) 2000 Elsevier Science B.V. All rights reserved.