A Portrait of Alzheimer Secretases--New Features and Familiar Faces

Abstract

The amyloid β-peptide (Aβ) 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 Aβ precursor protein (APP). The three proteases that cleave APP, α-, β-, and γ-secretases, have been implicated in the etiology of AD. β-Secretase is a membrane-anchored protein with clear homology to soluble aspartyl proteases, and α-secretase displays characteristics of certain membrane-tethered metalloproteases. γ-Secretase is apparently an oligomeric complex that includes the presenilins, which may be the catalytic component of this protease. Identification of the α-, β-, and γ-secretases provides potential targets for designing new drugs to treat AD.