DOI: 10.1073/pnas.160115697. BACE2, a β-secretase homolog, cleaves at the β site and within the amyloid-β region of the amyloid-β precursor protein

BACE2, a β-secretase homolog, cleaves at the β site and within the amyloid-β region of the amyloid-β precursor protein

10.1073/pnas.160115697

Crossref journal-article

Proceedings of the National Academy of Sciences

Proceedings of the National Academy of Sciences (341)

Abstract

Production of amyloid-β protein (Aβ) is initiated by a β-secretase that cleaves the Aβ precursor protein (APP) at the N terminus of Aβ (the β site). A recently identified aspartyl protease, BACE, cleaves the β site and at residue 11 within the Aβ region of APP. Here we show that BACE2, a BACE homolog, cleaves at the β site and more efficiently at a different site within Aβ. The Flemish missense mutation of APP, implicated in a form of familial Alzheimer's disease, is adjacent to this latter site and markedly increases Aβ production by BACE2 but not by BACE. BACE and BACE2 respond identically to conservative β-site mutations, and alteration of a common active site Arg inhibits β-site cleavage but not cleavage within Aβ by both enzymes. These data suggest that BACE2 contributes to Aβ production in individuals bearing the Flemish mutation, and that selective inhibition of these highly similar proteases may be feasible and therapeutically advantageous.

Bibliography

Farzan, M., Schnitzler, C. E., Vasilieva, N., Leung, D., & Choe, H. (2000). BACE2, a Î²-secretase homolog, cleaves at the Î² site and within the amyloid-Î² region of the amyloid-Î² precursor protein. Proceedings of the National Academy of Sciences, 97(17), 9712â9717.

Authors 5

Michael Farzan (first)
Christine E. Schnitzler (additional)
Natalya Vasilieva (additional)
Doris Leung (additional)
Hyeryun Choe (additional)

References 29 Referenced 315

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Dates

Type	When
Created	23 years ago (July 26, 2002, 10:40 a.m.)
Deposited	3 years, 4 months ago (April 13, 2022, 1:41 a.m.)
Indexed	1 day, 19 hours ago (Aug. 22, 2025, 12:45 a.m.)
Issued	25 years ago (Aug. 8, 2000)
Published	25 years ago (Aug. 8, 2000)
Published Online	25 years ago (Aug. 8, 2000)
Published Print	25 years ago (Aug. 15, 2000)

Funders 0

None

BibTeX

@article{Farzan_2000, title={BACE2, a β-secretase homolog, cleaves at the β site and within the amyloid-β region of the amyloid-β precursor protein}, volume={97}, ISSN={1091-6490}, url={http://dx.doi.org/10.1073/pnas.160115697}, DOI={10.1073/pnas.160115697}, number={17}, journal={Proceedings of the National Academy of Sciences}, publisher={Proceedings of the National Academy of Sciences}, author={Farzan, Michael and Schnitzler, Christine E. and Vasilieva, Natalya and Leung, Doris and Choe, Hyeryun}, year={2000}, month=aug, pages={9712–9717} }

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