Citation
Shi, Xiao-Ping, et al. "Novel Mutations Introduced at the Beta-site of Amyloid Beta Protein Precursor Enhance the Production of Amyloid Beta Peptide By BACE1 in Vitro and in Cells." Journal of Alzheimer's Disease : JAD, vol. 7, no. 2, 2005, pp. 139-48; discussion 173-80.
Shi XP, Tugusheva K, Bruce JE, et al. Novel mutations introduced at the beta-site of amyloid beta protein precursor enhance the production of amyloid beta peptide by BACE1 in vitro and in cells. J Alzheimers Dis. 2005;7(2):139-48; discussion 173-80.
Shi, X. P., Tugusheva, K., Bruce, J. E., Lucka, A., Chen-Dodson, E., Hu, B., Wu, G. X., Price, E., Register, R. B., Lineberger, J., Miller, R., Tang, M. J., Espeseth, A., Kahana, J., Wolfe, A., Crouthamel, M. C., Sankaranarayanan, S., Simon, A., Chen, L., ... Hazuda, D. J. (2005). Novel mutations introduced at the beta-site of amyloid beta protein precursor enhance the production of amyloid beta peptide by BACE1 in vitro and in cells. Journal of Alzheimer's Disease : JAD, 7(2), 139-48; discussion 173-80.
Shi XP, et al. Novel Mutations Introduced at the Beta-site of Amyloid Beta Protein Precursor Enhance the Production of Amyloid Beta Peptide By BACE1 in Vitro and in Cells. J Alzheimers Dis. 2005;7(2):139-48; discussion 173-80. PubMed PMID: 15851852.
TY - JOUR
T1 - Novel mutations introduced at the beta-site of amyloid beta protein precursor enhance the production of amyloid beta peptide by BACE1 in vitro and in cells.
AU - Shi,Xiao-Ping,
AU - Tugusheva,Katherine,
AU - Bruce,James E,
AU - Lucka,Adam,
AU - Chen-Dodson,Elizabeth,
AU - Hu,Binghua,
AU - Wu,Guo-Xin,
AU - Price,Eric,
AU - Register,Robert B,
AU - Lineberger,Janet,
AU - Miller,Ron,
AU - Tang,Mei-Jy,
AU - Espeseth,Amy,
AU - Kahana,Jason,
AU - Wolfe,Abigail,
AU - Crouthamel,Ming-Chih,
AU - Sankaranarayanan,Sethu,
AU - Simon,Adam,
AU - Chen,Lin,
AU - Lai,Ming-Tain,
AU - Pietrak,Beth,
AU - DiMuzio,Jillian,
AU - Li,Yueming,
AU - Xu,Min,
AU - Huang,Qian,
AU - Garsky,Victor,
AU - Sardana,Mohinder K,
AU - Hazuda,Daria J,
PY - 2005/4/27/pubmed
PY - 2005/8/16/medline
PY - 2005/4/27/entrez
SP - 139-48; discussion 173-80
JF - Journal of Alzheimer's disease : JAD
JO - J Alzheimers Dis
VL - 7
IS - 2
N2 - Abnormal production and accumulation of amyloid-beta peptide (Abeta) plays a major role in the pathogenesis of Alzheimer's disease (AD). beta-secretase (BACE1) is responsible for the cleavage at thebeta-site in amyloid beta protein precursor (AbetaPP/APP) to generate the N-terminus of Abeta. Here we report the stepwise identification and characterization of a novel APP-beta-site mutant, "NFEV" (APP_NFEV) in vitro and in cells. In vitro, the APP_NFEV exhibits 100-fold enhanced cleavage rate relative to the "wild-type" substrate (APPwt) and 10-fold increase relative to the Swedish-type mutation variant (APPsw). In cells, it was preferably cleaved among 24 APP beta-site mutations tested. More importantly, the APP_NFEV mutant failed to generate any detectable Abeta peptides in BACE1-KO mouse fibroblast cells. The production of Abeta peptides was restored by co-transfecting human BACE1, demonstrating that BACE1 is the only enzyme responsible for the processing of APP_NFEV in these cells. Analysis of APP_NFEV cleavage products secreted in the media revealed that in cells BACE1 cleaves APP_NFEV at the position between NF and EV, identical to that observed in vitro. A BACE inhibitor blocked the processing of the APP_NFEV beta-site in vitro and in cells. Our data indicates that the "NFEV" mutant is not only an enhanced substrate for BACE1 in vitro, but also a specific substrate for BACE1 in cells.
SN - 1387-2877
UR - https://www.unboundmedicine.com/medline/citation/15851852/Novel_mutations_introduced_at_the_beta_site_of_amyloid_beta_protein_precursor_enhance_the_production_of_amyloid_beta_peptide_by_BACE1_in_vitro_and_in_cells_
L2 - https://content.iospress.com/openurl?genre=article&issn=1387-2877&volume=7&issue=2&spage=139
DB - PRIME
DP - Unbound Medicine
ER -