| Autor: |
Dreyer, Robert N., Bausch, Kathryn M., Fracasso, Paul, Hammond, Lisa J., Wunderlich, David, Wirak, Dana O., Davis, Gary, Brini, Carla M., Buckholz, Thomas M., König, Gerhard, Kamarck, Michael E., Tamburini, Paul P. |
| Předmět: |
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| Zdroj: |
European Journal of Biochemistry; 9/1/94, Vol. 224 Issue 2, p265-271, 7p |
| Abstrakt: |
A major pre-β-amyloid protein695 (APP695) processing activity from Alzheimer's disease brain extracts was identified and found to be indistinguishable from the activity of cathepsin D.APP695 processing activity cleaved APP695 into a series of fragments that reacted on immunoblots to a monoclonal antibody (C286.8a) against β-amyloid-(1-7)-peptide and cleaved N-dansyl-APP-(591601)-amide at the Glu-Val and Met-Asp bonds. Fragments of 5.5 kDa and 10-12 kDa were formed from the cleavage of APP695 by cathepsin D at the Glu593-Va1594 bond. and had the same Nterminus as a minor form of β-amyloid released by cells. The Lys595→Asn and Met596→Leu substitutions found in a pedigree of familial Alzheimer's disease, increased the cathepsin D-catalyzed rate of accumulation of 5.5 kDa and 10-12 kDa C286.8a-reactive fragments 5-10 fold. This substitution also increased the rate of N-dansyl-APP4591-601)-amide cleavage at the Xaa-Asp bond by up to 41-fold. These observations suggest a role of cathepsin D in β-amyloid formation under certain circumstances. [ABSTRACT FROM AUTHOR] |
| Databáze: |
Complementary Index |
| Externí odkaz: |
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