Nonsteroidal anti-inflammatory drugs can lower amyloidogenic Aβ42 by inhibiting Rho

被引：277

作者：

Zhou, Y ^{[1
]}

Su, Y ^{[1
]}

Li, BL ^{[1
]}

Liu, F ^{[1
]}

Ryder, JW ^{[1
]}

Wu, X ^{[1
]}

Gonzalez-DeWhitt, PA ^{[1
]}

Gelfanova, V ^{[1
]}

Hale, JE ^{[1
]}

May, PC ^{[1
]}

Paul, SM ^{[1
]}

Ni, BH ^{[1
]}

机构：

[1] Eli Lilly & Co, Lilly Res Labs, Neurosci Discovery Res & Biores Technol & Prot, Indianapolis, IN 46285 USA

来源：

SCIENCE | 2003年 / 302卷 / 5648期

关键词：

D O I：

10.1126/science.1090154

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

A subset of nonsteroidal anti-inflammatory drugs (NSAIDs) has been shown to preferentially reduce the secretion of the highly amyloidogenic, 42-residue amyloid-beta peptide Abeta(42). We found that Rho and its effector, Rho-associated kinase, preferentially regulated the amount of Abeta(42) produced in vitro and that only those NSAIDs effective as Rho inhibitors lowered Abeta(42). Administration of Y-27632, a selective Rock inhibitor, also preferentially lowered brain levels of Abeta(42) in a transgenic mouse model of Alzheimer's disease. Thus, the Rho-Rock pathway may regulate amyloid precursor protein processing, and a subset of NSAIDs can reduce Abeta(42) through inhibition of Rho activity.

引用

页码：1215 / 1217

页数：3

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