Proteases involved in the processing of the Alzheimer's disease amyloid precursor protein

We describe the characterization of a protease having alpha-secretase activity that cleaves Alzheimer's disease amyloid precursor protein (APP) in vitro. This enzyme activity is extremely high in rat liver lysosomes. The cleavage enzyme belongs to a cysteine protease family, and is sensitive to CA-074, indicating that the enzyme is identical to cathepsin B. Recently, racemization of the Asp residues in amyloid beta protein has been reported to be important in the deposition of the beta protein. A novel D-aspartyl endopeptidase was found and purified from rat liver mitochondria. Whether cathepsin B and this endopeptidase participate in vivo in the metabolism of APP or beta protein during pathological conditions remains to be determined.