Biomedicine - A portrait of Alzheimer secretases - New features and familiar faces

The amyloid beta -peptide (A beta) is a principal component of the cerebral plaques found in the brains of patients with Alzeheimer's disease (AD). Th is insoluble 40- to 42-amino acid peptide is formed by the cleavage of the A beta 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 solu ble aspartyl proteases, and alpha -secretase displays characteristics of ce rtain membrane-tethered metalloproteases. gamma -Secretase is apparently an oligomeric complex that includes the presenilins, which may be the catalyt ic component of this protease. Identification of the alpha-, beta-, and gam ma -secretases provides potential targets for designing new drugs to treat AD.