A portrait of Alzheimer secretases--new features and familiar faces

Abstract

The amyloid beta-peptide (Abeta) is a principal component of the cerebral plaques found in the brains of patients with Alzeheimer's disease (AD). This insoluble 40- to 42-amino acid peptide is formed by the cleavage of the Abeta precursor protein (APP). The three proteases that cleave APP, alpha-, beta-, and gamma-secretases, have been implicated in the etiology of AD. beta-Secretase is a membrane-anchored protein with clear homology to soluble aspartyl proteases, and alpha-secretase displays characteristics of certain membrane-tethered metalloproteases. gamma-Secretase is apparently an oligomeric complex that includes the presenilins, which may be the catalytic component of this protease. Identification of the alpha-, beta-, and gamma-secretases provides potential targets for designing new drugs to treat AD.