β-Secretase Cleavage of Alzheimer's Amyloid Precursor Protein by the Transmembrane Aspartic Protease BACE
Year: 1999
Type: article
Abstract: Cerebral deposition of amyloid beta peptide (Abeta) is an early and critical feature of Alzheimer's disease. Abeta generation depends on proteolytic cleavage of the amyloid precursor protein (APP) by two unknown proteases: beta-secretase and gamma-secretase. These proteases are prime therapeutic targets. A transmembrane aspartic protease with all the known characteristics of beta-secretase was cloned and characterized. Overexpression of this protease, termed BACE (for beta-site APP-cleaving enzyme) increased the amount of beta-secretase cleavage products, and these were cleaved exactly and only at known beta-secretase positions. Antisense inhibition of endogenous BACE messenger RNA decreased the amount of beta-secretase cleavage products, and purified BACE protein cleaved APP-derived substrates with the same sequence specificity as beta-secretase. Finally, the expression pattern and subcellular localization of BACE were consistent with that expected for beta-secretase. Future development of BACE inhibitors may prove beneficial for the treatment of Alzheimer's disease.
Source: Science
Authors: Robert Vassar, Brian D. Bennett, Safura Babu-Khan, Steve Kahn, Elizabeth A. Mendiaz, Paul Denis, David B. Teplow, Sandra Ross, Patricia Amarante, Richard Loeloff, Yi Luo, Seth Fisher, Janis Fuller, Steven Edenson, Jackson Lile, Mark A. Jarosinski, Anja Leona Biere, Eileen Curran, Teresa Burgess, Jean-Claude Louis, Frank Collins, James Treanor, Gary Rogers, Martin Citron
Language: English
Subfield: Physiology
Field: Medicine
Domain: Health Sciences
Open Access status: green
OpenAlex ID: W2133019124