The AβCs of Aβ-cleaving Proteases

The amyloid beta-protein (A beta), which accumulates abnormally in Alzheimer disease (AD), is degraded by a diverse set of proteolytic enzymes. A beta-cleaving proteases, largely ignored until only recently, are now known to play a pivotal role in the regulation of cerebral A beta levels and amyloid plaque formation in animal models, and accumulating evidence suggests that defective A beta proteolysis may be operative in many AD cases. This review summarizes the growing body of evidence supporting the involvement of specific A beta-cleaving proteases in the etiology and potential treatment of AD. Recognition of the importance of A beta degradation to the overall economy of A beta has revised our thinking about the mechanistic basis of AD pathogenesis and identified a novel class of enzymes that may serve as both therapeutic targets and therapeutic agents.