机构:Univ Tokyo, Dept Life Sci, Grad Sch Arts & Sci, Meguro Ku, Tokyo 1538902, Japan
Hattori, C
Asai, M
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机构:Univ Tokyo, Dept Life Sci, Grad Sch Arts & Sci, Meguro Ku, Tokyo 1538902, Japan
Asai, M
Oma, Y
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机构:Univ Tokyo, Dept Life Sci, Grad Sch Arts & Sci, Meguro Ku, Tokyo 1538902, Japan
Oma, Y
Kino, Y
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机构:Univ Tokyo, Dept Life Sci, Grad Sch Arts & Sci, Meguro Ku, Tokyo 1538902, Japan
Kino, Y
Sasagawa, N
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机构:Univ Tokyo, Dept Life Sci, Grad Sch Arts & Sci, Meguro Ku, Tokyo 1538902, Japan
Sasagawa, N
Saido, TC
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机构:Univ Tokyo, Dept Life Sci, Grad Sch Arts & Sci, Meguro Ku, Tokyo 1538902, Japan
Saido, TC
Maruyama, K
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机构:Univ Tokyo, Dept Life Sci, Grad Sch Arts & Sci, Meguro Ku, Tokyo 1538902, Japan
Maruyama, K
Ishiura, S
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机构:
Univ Tokyo, Dept Life Sci, Grad Sch Arts & Sci, Meguro Ku, Tokyo 1538902, JapanUniv Tokyo, Dept Life Sci, Grad Sch Arts & Sci, Meguro Ku, Tokyo 1538902, Japan
Ishiura, S
[1
]
机构:
[1] Univ Tokyo, Dept Life Sci, Grad Sch Arts & Sci, Meguro Ku, Tokyo 1538902, Japan
[2] RIKEN, Brain Sci Inst, Wako, Saitama 3510198, Japan
[3] Saitama Med Sch, Dept Pharmacol, Moroyama, Saitama 3500495, Japan
Alzheimer's disease;
APP;
A beta;
beta-secretase;
gamma-secretase;
BACE1;
nicastrin;
D O I:
10.1016/S0006-291X(02)00351-0
中图分类号:
Q5 [生物化学];
Q7 [分子生物学];
学科分类号:
071010 ;
081704 ;
摘要:
beta-Amyloid peptide (Abeta) is generated through the proteolytic cleavage of beta-amyloid precursor protein (APP) by beta- and gamma-secretases. The beta-secretase, BACE1, initiates Abeta formation followed by gamma-cleavage within the APP transmembrane domain. Although BACE1 localizes in the transGolgi network (TGN), its physiological substrates and modulators are not known, In addition, the relationship to other secretase(s) also remains unidentified. Here, we demonstrate that BACE1 binds to nicastrin, a component of gamma-secretase complexes, in vitro, and that nicastrin activates beta-secretase activity in COS-7 cells. (C) 2002 Elsevier Science (USA). All rights reserved.