BACE1 and Presenilin: Two Unusual Aspartyl Proteases Involved in Alzheimer's Disease

被引:27
作者
Dominguez, Diana-Ines [1 ]
Hartmann, Dieter
De Strooper, Bart
机构
[1] VIB4, Dept Menselijke Erfelijkheid, Mol Genet Sect, BE-3000 Louvain, Belgium
关键词
Alzheimer's disease; Knockout mice; beta-Secretase; gamma-Secretase;
D O I
10.1159/000080982
中图分类号
R74 [神经病学与精神病学];
学科分类号
摘要
Two enzymatic activities are required to generate the pathogenic beta-amyloid (A beta) peptide that accumulates in the brain of Alzheimer's disease patients. Both activities are carried out by two unusual aspartyl proteases known as beta- and gamma-secretase. Their therapeutic inhibition appears, therefore, a promising strategy to treat the disease. Transgenic mouse models in which the genes encoding the secretases have been ablated offer an invaluable tool, on the one hand, to gain more insights into the biological function of these proteases and, on the other hand, to predict the consequences that might be associated with enzyme inhibition in vivo. Copyright (C) 2004 S. Karger AG, Basel
引用
收藏
页码:168 / 174
页数:7
相关论文
共 81 条
[1]   The gene encoding DRAP (BACE2), a glycosylated transmembrane protein of the aspartic protease family, maps to the Down critical region [J].
Acquati, F ;
Accarino, M ;
Nucci, C ;
Fumagalli, P ;
Jovine, L ;
Ottolenghi, S ;
Taramelli, R .
FEBS LETTERS, 2000, 468 (01) :59-64
[2]  
Annaert W, 2000, ANN NY ACAD SCI, V920, P158
[3]   BACE-2 is overexpressed in Down's syndrome [J].
Barbiero, L ;
Benussi, L ;
Ghidoni, R ;
Alberici, A ;
Russo, C ;
Schettini, G ;
Pagano, SF ;
Parati, EA ;
Mazzoli, F ;
Nicosia, F ;
Signorini, S ;
Feudatari, E ;
Binetti, G .
EXPERIMENTAL NEUROLOGY, 2003, 182 (02) :335-345
[4]   Antagonistic effects of β-site amyloid precursor protein-cleaving enzymes 1 and 2 on β-amyloid peptide production in cells [J].
Basi, G ;
Frigon, N ;
Barbour, R ;
Doan, T ;
Gordon, G ;
McConlogue, L ;
Sinha, S ;
Zeller, M .
JOURNAL OF BIOLOGICAL CHEMISTRY, 2003, 278 (34) :31512-31520
[5]   Expression analysis of BACE2 in brain and peripheral tissues [J].
Bennett, BD ;
Babu-Khan, S ;
Loeloff, R ;
Louis, JC ;
Curran, E ;
Citron, M ;
Vassar, R .
JOURNAL OF BIOLOGICAL CHEMISTRY, 2000, 275 (27) :20647-20651
[6]   ADAMs: focus on the protease domain [J].
Black, RA ;
White, JM .
CURRENT OPINION IN CELL BIOLOGY, 1998, 10 (05) :654-659
[7]   Regulated intramembrane proteolysis: A control mechanism conserved from bacteria to humans [J].
Brown, MS ;
Ye, J ;
Rawson, RB ;
Goldstein, JL .
CELL, 2000, 100 (04) :391-398
[8]   BACE1 is the major β-secretase for generation of Aβ peptides by neurons [J].
Cai, HB ;
Wang, YS ;
McCarthy, D ;
Wen, HJ ;
Borchelt, DR ;
Price, DL ;
Wong, PC .
NATURE NEUROSCIENCE, 2001, 4 (03) :233-234
[9]   Apical sorting of β-secretase limits amyloid β-peptide production [J].
Capell, A ;
Meyn, L ;
Fluhrer, R ;
Teplow, DB ;
Walter, J ;
Haass, C .
JOURNAL OF BIOLOGICAL CHEMISTRY, 2002, 277 (07) :5637-5643
[10]   Exclusively targeting β-secretase to lipid rafts by GPI-anchor addition up-regulates β-site processing of the amyloid precursor protein [J].
Cordy, JM ;
Hussain, I ;
Dingwall, C ;
Hooper, NM ;
Turner, AJ .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2003, 100 (20) :11735-11740