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BACE2, a beta -secretase homolog, cleaves at the beta site and within the amyloid-beta region of the amyloid-beta precursor protein.
Proc Natl Acad Sci U S A. 2000 Aug 15; 97(17):9712-7.PN

Abstract

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

Authors+Show Affiliations

Department of Cancer Immunology and AIDS, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA 02115, USA. farzan@mbcrr.harvard.eduNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article

Language

eng

PubMed ID

10931940

Citation

Farzan, M, et al. "BACE2, a Beta -secretase Homolog, Cleaves at the Beta Site and Within the Amyloid-beta Region of the Amyloid-beta Precursor Protein." Proceedings of the National Academy of Sciences of the United States of America, vol. 97, no. 17, 2000, pp. 9712-7.
Farzan M, Schnitzler CE, Vasilieva N, et al. BACE2, a beta -secretase homolog, cleaves at the beta site and within the amyloid-beta region of the amyloid-beta precursor protein. Proc Natl Acad Sci U S A. 2000;97(17):9712-7.
Farzan, M., Schnitzler, C. E., Vasilieva, N., Leung, D., & Choe, H. (2000). BACE2, a beta -secretase homolog, cleaves at the beta site and within the amyloid-beta region of the amyloid-beta precursor protein. Proceedings of the National Academy of Sciences of the United States of America, 97(17), 9712-7.
Farzan M, et al. BACE2, a Beta -secretase Homolog, Cleaves at the Beta Site and Within the Amyloid-beta Region of the Amyloid-beta Precursor Protein. Proc Natl Acad Sci U S A. 2000 Aug 15;97(17):9712-7. PubMed PMID: 10931940.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - BACE2, a beta -secretase homolog, cleaves at the beta site and within the amyloid-beta region of the amyloid-beta precursor protein. AU - Farzan,M, AU - Schnitzler,C E, AU - Vasilieva,N, AU - Leung,D, AU - Choe,H, PY - 2000/8/10/pubmed PY - 2000/9/23/medline PY - 2000/8/10/entrez SP - 9712 EP - 7 JF - Proceedings of the National Academy of Sciences of the United States of America JO - Proc Natl Acad Sci U S A VL - 97 IS - 17 N2 - Production of amyloid-beta protein (Abeta) is initiated by a beta-secretase that cleaves the Abeta precursor protein (APP) at the N terminus of Abeta (the beta site). A recently identified aspartyl protease, BACE, cleaves the beta site and at residue 11 within the Abeta region of APP. Here we show that BACE2, a BACE homolog, cleaves at the beta site and more efficiently at a different site within Abeta. The Flemish missense mutation of APP, implicated in a form of familial Alzheimer's disease, is adjacent to this latter site and markedly increases Abeta production by BACE2 but not by BACE. BACE and BACE2 respond identically to conservative beta-site mutations, and alteration of a common active site Arg inhibits beta-site cleavage but not cleavage within Abeta by both enzymes. These data suggest that BACE2 contributes to Abeta production in individuals bearing the Flemish mutation, and that selective inhibition of these highly similar proteases may be feasible and therapeutically advantageous. SN - 0027-8424 UR - https://www.unboundmedicine.com/medline/citation/10931940/BACE2_a_beta__secretase_homolog_cleaves_at_the_beta_site_and_within_the_amyloid_beta_region_of_the_amyloid_beta_precursor_protein_ L2 - http://www.pnas.org/cgi/pmidlookup?view=long&pmid=10931940 DB - PRIME DP - Unbound Medicine ER -