A Novel Approach for Characterization of Cathepsin D Protease and Its Effect on Tau and [beta]-Amyloid Proteins

• Published in: Neurochemical research 2011-05, Vol.36 (5), p.754
• Main Authors: Malik, Mazhar, Fenko, Michael D, Sheikh, Ashfaq M, Wen, Guang, Li, Xiaohong
• Format: Article
• Language: English
• ISSN: 0364-3190; 1573-6903
• DOI: 10.1007/s11064-010-0395-9

Cathepsin D is the lysosomal protease abundantly expressed in the brain. It plays an important role in the regulation of cellular apoptosis. In addition, cathepsin D has been shown to be involved in the pathogenesis of Alzheimer disease and autism. In this study, we developed a novel approach for the preparation of highly purified cathepsin D from the calf brain. This high grade purification is achieved by using DEAE-Sephacel Chromatography before the final step of applying to the Pepstatin-Sepharose 4B column. The properties of cathepsin D have also been studied. We show that cathepsin D cleaves both tau and β-amyloid precursor protein (APP). Both tau and APP are involved in the pathogenesis of Alzheimer's disease. Our findings strongly suggest a link between the lysosomal dysfunction of cathepsin D and the etiology of Alzheimer's disease. Our findings also indicate that cathepsin D could be a new approach to treating Alzheimer's disease.[PUBLICATION ABSTRACT]