Adaptor protein interactions: modulators of amyloid precursor protein metabolism and Alzheimer's disease risk?

被引：132

作者：

King, GD

Turner, RS

机构：

[1] Vet Affairs Healthcare Syst, Geriatr Res Educ & Clin Ctr, Ann Arbor, MI 48105 USA

[2] Univ Michigan, Neurosci Program, Ann Arbor, MI 48105 USA

[3] Univ Michigan, Dept Neurol, Ann Arbor, MI 48105 USA

来源：

EXPERIMENTAL NEUROLOGY | 2004年 / 185卷 / 02期

关键词：

Alzheimer's disease; amyloid precursor protein; A beta; beta-secretase; gamma-secretase; adaptor proteins; XII; mint; Fe65; JIP; PTB domain;

D O I：

10.1016/j.expneurol.2003.10.011

中图分类号：

Q189 [神经科学];

学科分类号：

071006 ;

摘要：

The cytoplasmic C-terminus of APP plays critical roles in its cellular trafficking and delivery to proteases. Adaptor proteins with phosphotyrosine-binding (PTB) domains, including those in the XI 1, Fe65, and c-Jun N-terminal kinase (JNK)-interacting protein (JIP) families, bind specifically to the absolutely conserved -YENPTY- motif in the APP C-terminus to regulate its trafficking and processing. Compounds that modulate APP-adaptor protein interactions may inhibit Abeta generation by specifically targeting the substrate (APP) instead of the enzyme (beta or gamma-secretase). Genetic polymorphisms in (or near) adaptor proteins may influence risk of sporadic AD by interacting with APP in vivo to modulate its trafficking and processing to Abeta. (C) 2003 Elsevier Inc. All rights reserved.

引用

页码：208 / 219

页数：12

共 155 条

[1] Treatment of ischemic brain damage by perturbing NMDA receptor-PSD-95 protein interactions [J].