BACE1 and presenilin: two unusual aspartyl proteases involved in Alzheimer's disease

Abstract

Two enzymatic activities are required to generate the pathogenic beta-amyloid (Abeta) peptide that accumulates in the brain of Alzheimer's disease patients. Both activities are carried out by two unusual aspartyl proteases known as beta- and gamma-secretase. Their therapeutic inhibition appears, therefore, a promising strategy to treat the disease. Transgenic mouse models in which the genes encoding the secretases have been ablated offer an invaluable tool, on the one hand, to gain more insights into the biological function of these proteases and, on the other hand, to predict the consequences that might be associated with enzyme inhibition in vivo.