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
[51]   AMINO-TERMINAL DELETIONS ENHANCE AGGREGATION OF BETA-AMYLOID PEPTIDES IN-VITRO [J].
PIKE, CJ ;
OVERMAN, MJ ;
COTMAN, CW .
JOURNAL OF BIOLOGICAL CHEMISTRY, 1995, 270 (41) :23895-23898
[52]   β-secretase (BACE) and GSK-3 mRNA levels in Alzheimer's disease [J].
Preece, P ;
Virley, DJ ;
Costandi, M ;
Coombes, R ;
Moss, SJ ;
Mudge, AW ;
Jazin, E ;
Cairns, NJ .
MOLECULAR BRAIN RESEARCH, 2003, 116 (1-2) :155-158
[53]   The ADAM gene family - surface proteins with adhesion and protease activity [J].
Primakoff, P ;
Myles, DG .
TRENDS IN GENETICS, 2000, 16 (02) :83-87
[54]   Ceramide stabilizes β-site amyloid precursor protein-cleaving enzyme 1 and promotes amyloid β-peptide biogenesis (Withdrawn Publication. See vol. 298, 2022) (Withdrawn Publication. See vol. 298, 2022) [J].
Puglielli, L ;
Ellis, BC ;
Saunders, AJ ;
Kovacs, DM .
JOURNAL OF BIOLOGICAL CHEMISTRY, 2003, 278 (22) :19777-19783
[55]   Compartmentalization of β-secretase (Asp2) into low-buoyant density, noncaveolar lipid rafts [J].
Riddell, DR ;
Christie, G ;
Hussain, I ;
Dingwall, C .
CURRENT BIOLOGY, 2001, 11 (16) :1288-1293
[56]   BACE knockout mice are healthy despite lacking the primary β-secretase activity in brain:: implications for Alzheimer's disease therapeutics [J].
Roberds, SL ;
Anderson, J ;
Basi, G ;
Bienkowski, MJ ;
Branstetter, DG ;
Chen, KS ;
Freedman, SB ;
Frigon, NL ;
Games, D ;
Hu, K ;
Johnson-Wood, K ;
Kappenman, KE ;
Kawabe, TT ;
Kola, I ;
Kuehn, R ;
Lee, M ;
Liu, WQ ;
Motter, R ;
Nichols, NF ;
Power, M ;
Robertson, DW ;
Schenk, D ;
Schoor, M ;
Shopp, GM ;
Shuck, ME ;
Sinha, S ;
Svensson, KA ;
Tatsuno, G ;
Tintrup, H ;
Wijsman, J ;
Wright, S ;
McConlogue, L .
HUMAN MOLECULAR GENETICS, 2001, 10 (12) :1317-1324
[57]   Differential utilization of upstream AUGs in the β-secretase mRNA suggests that a shunting mechanism regulates translation [J].
Rogers, GW ;
Edelman, GM ;
Mauro, VP .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2004, 101 (09) :2794-2799
[58]  
Schlöndorff J, 1999, J CELL SCI, V112, P3603
[59]   Heparan sulfate regulates amyloid precursor protein processing by BACE1, the Alzheimer's β-secretase [J].
Scholefield, Z ;
Yates, EA ;
Wayne, G ;
Amour, A ;
McDowell, W ;
Turnbull, JE .
JOURNAL OF CELL BIOLOGY, 2003, 163 (01) :97-107
[60]   Notch and presenilins in vertebrates and invertebrates: implications for neuronal development and degeneration [J].
Selkoe, DJ .
CURRENT OPINION IN NEUROBIOLOGY, 2000, 10 (01) :50-57