A protein farnesyltransferase inhibitor ameliorates disease in a mouse model of progeria

被引：249

作者：

Fong, LG ^{[1
]}

Frost, D

Meta, M

Qiao, X

Yang, SH

Coffinier, C

Young, SG

机构：

[1] Univ Calif Los Angeles, David Geffen Sch Med, Dept Med, Div Cardiol, Los Angeles, CA 90095 USA

[2] Abbott Labs, Abbott Pk, IL 60064 USA

[3] Univ Calif San Francisco, Dept Radiol, San Francisco, CA 94107 USA

来源：

SCIENCE | 2006年 / 311卷 / 5767期

关键词：

D O I：

10.1126/science.1124875

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：

Progerias are rare genetic diseases characterized by premature aging. Several progeroid disorders are caused by mutations that lead to the accumulation of a lipid-modified (farnesylated) form of prelamin A, a protein that contributes to the structural scaffolding for the cell nucleus. In progeria, the accumulation of farnesyl-prelamin A disrupts this scaffolding, leading to misshapen nuclei. Previous studies have shown that farnesyltransferase inhibitors (FTIs) reverse this cellular abnormality. We tested the efficacy of an FTI (ABT-100) in Zmpste24-deficient mice, a mouse model of progeria. The FTI-treated mice exhibited improved body weight, grip strength, bone integrity, and percent survival at 20 weeks of age. These results suggest that FTIs may have beneficial effects in humans with progeria.

引用

页码：1621 / 1623

页数：3

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