Structure and function of γ-secretase

被引：75

作者：

Tolia, Alexandra

De Strooper, Bart ^{[1
]}

机构：

[1] Katholieke Univ Leuven, Ctr Human Genet, B-3000 Louvain, Belgium

来源：

SEMINARS IN CELL & DEVELOPMENTAL BIOLOGY | 2009年 / 20卷 / 02期

关键词：

Presenilin; gamma-Secretase complex; Regulated intramembrane proteolysis; Alzheimer's disease; Catalysis; Aspartic protease; AMYLOID PRECURSOR PROTEIN; NONSTEROIDAL ANTIINFLAMMATORY DRUGS; SIGNAL PEPTIDE PEPTIDASE; FAMILY INTRAMEMBRANE PROTEASE; C-TERMINAL FRAGMENT; ALZHEIMERS-DISEASE; TRANSMEMBRANE DOMAIN; CATALYTIC PORE; BETA-PROTEIN; IN-VIVO;

D O I：

10.1016/j.semcdb.2008.10.007

中图分类号：

Q2 [细胞生物学];

学科分类号：

071009 ; 090102 ;

摘要：

The gamma-secretase complex is a prime target for pharmacological intervention in Alzheimer's disease and so far drug discovery efforts have yielded a large variety of potent and rather specific inhibitors of this enzymatic activity. However, as gamma-secretase is able to cleave a wide variety of physiological important substrates, the real challenge is to develop substrate-specific compounds. Therefore, obtaining structural information about gamma-secretase is indispensable. As crystal structures of the complex will be difficult to achieve, applied biochemical approaches need to be integrated with structural information obtained from other intramembrane-cleaving proteases. Here we review current knowledge about the structure and function of gamma-secretase and discuss the value of these findings for the mechanistic understanding of this unusual protease. (C) 2008 Elsevier Ltd. All rights reserved.

引用

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页码：211 / 218

页数：8

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