非甾体抗炎药可通过抑制Rho降低淀粉样β42蛋白水平。

Nonsteroidal anti-inflammatory drugs can lower amyloidogenic Abeta42 by inhibiting Rho.

作者信息

Zhou Yan, Su Yuan, Li Baolin, Liu Feng, Ryder John W, Wu Xin, Gonzalez-DeWhitt Patricia A, Gelfanova Valentina, Hale John E, May Patrick C, Paul Steven M, Ni Binhui

机构信息

Neuroscience Discovery Research and Bioresearch Technologies and Proteins, Lilly Research Laboratories, Eli Lilly and Company, Indianapolis, IN 46285, USA.

出版信息

Science. 2003 Nov 14;302(5648):1215-7. doi: 10.1126/science.1090154.

DOI:10.1126/science.1090154

PMID:14615541

Abstract

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 Abeta42. We found that Rho and its effector, Rho-associated kinase, preferentially regulated the amount of Abeta42 produced in vitro and that only those NSAIDs effective as Rho inhibitors lowered Abeta42. Administration of Y-27632, a selective Rock inhibitor, also preferentially lowered brain levels of Abeta42 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 Abeta42 through inhibition of Rho activity.

摘要

已证实，一部分非甾体抗炎药（NSAIDs）能优先减少具有高度淀粉样蛋白生成性的42个氨基酸残基的β淀粉样肽Aβ42的分泌。我们发现，Rho及其效应器Rho相关激酶优先调节体外产生的Aβ42的量，并且只有那些作为Rho抑制剂有效的NSAIDs能降低Aβ42。给予选择性Rho相关激酶（Rock）抑制剂Y-27632，也能优先降低阿尔茨海默病转基因小鼠模型大脑中的Aβ42水平。因此，Rho-Rock信号通路可能调节淀粉样前体蛋白的加工过程，一部分NSAIDs可通过抑制Rho活性来降低Aβ42水平。