A novel approach for characterization of cathepsin D protease and its effect on tau and β-amyloid proteins.
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.
Department of Neurochemistry, NY State Institute for Basic Research in Developmental Disabilities, 1050 Forest Hill Road, Staten Island New York, NY 10314, USA.
Mazhar
M
Malik
Michael D
MD
Fenko
Ashfaq M
AM
Sheikh
Guang
G
Wen
Xiaohong
X
Li
D016229:Amyloid beta-Peptides / Q000378:metabolism*; D000818:Animals; D002402:Cathepsin D / Q000378:metabolism*; D002417:Cattle; D016875:tau Proteins / Q000378:metabolism*
D016229:Amyloid beta-Peptides; D016875:tau Proteins; D002402:Cathepsin D
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