Nonsteroidal anti-inflammatory drugs lower Aβ42 and change presenilin 1 conformation

被引：175

作者：

Lleó, A ^{[1
]}

Berezovska, O ^{[1
]}

Herl, L ^{[1
]}

Raju, S ^{[1
]}

Deng, A ^{[1
]}

Bacskai, BJ ^{[1
]}

Frosch, MP ^{[1
]}

Irizarry, M ^{[1
]}

Hyman, BT ^{[1
]}

机构：

[1] Massachusetts Gen Hosp, Alzheimers Res Unit, Charlestown, MA 02129 USA

来源：

NATURE MEDICINE | 2004年 / 10卷 / 10期

关键词：

D O I：

10.1038/nm1112

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：

Recent reports suggest that some commonly used nonsteroidal anti-inflammatory drugs (NSAIDs) unexpectedly shift the cleavage products of amyloid precursor protein (APP) to shorter, less fibrillogenic forms, although the underlying mechanism remains unknown. We now demonstrate, using a fluorescence resonance energy transfer method, that Abeta(42)-lowering NSAIDs specifically affect the proximity between APP and presenilin 1 and alter presenilin 1 conformation both in vitro and in vivo, suggesting a novel allosteric mechanism of action.

引用

页码：1065 / 1066

页数：2

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