Aph-1, Pen-2, and nicastrin with presenilin generate an active γ-secretase complex

被引：792

作者：

De Strooper, B

机构：

[1] Katholieke Univ Leuven, Ctr Human Genet, Neuronal Cell Biol & Gene Transfer Lab, Louvain, Belgium

[2] Flanders Interuniv Inst Biotechnol, Louvain, Belgium

来源：

NEURON | 2003年 / 38卷 / 01期

关键词：

D O I：

10.1016/S0896-6273(03)00205-8

中图分类号：

Q189 [神经科学];

学科分类号：

071006 ;

摘要：

gamma-Secretase cleaves the Amyloid Precursor Protein (APP) in its transmembrane domain, releasing the amyloid peptide AD. AD is the main constituent of the amyloid plaques in the brains of patients suffering from Alzheimer's disease. Several other type I integral membrane proteins are also cleaved by this protease. Recent work indicates that gamma-Secretase is a multiprotein complex consisting of Presenilin, Nicastrin, Aph-1, and Pen-2 and that all four proteins are necessary for full proteolytic activity. Since several paralogs and alternatively spliced variants of at least Presenilin and Aph-1 have been identified as well, it is anticipated that gamma-Secretase is not a homogeneous activity. gamma-Secretase is an interesting but complex drug target that challenges classical thinking about proteolytic processing and intracellular signaling.

引用

页码：9 / 12

页数：4

共 22 条

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