A protein farnesyltransferase inhibitor ameliorates disease in a mouse model of progeria
A protein farnesyltransferase inhibitor ameliorates disease in a mouse model of progeria
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DOI：
10.1126/science.1124875
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发表时间：
2006-03-17
期刊：
影响因子：
56.9
通讯作者：
Young, SG
中科院分区：
文献类型：
--
作者：
Fong, LG;Frost, D;Young, SG
早衰症是一种罕见的以过早衰老为特征的遗传性疾病。一些类孕症是由突变引起的，这些突变导致脂质修饰(法尼化)形式的前层蛋白A积累，这是一种有助于细胞核结构支架的蛋白质。在早衰症中，法尼基-前层蛋白A的积累破坏了这种支架，导致细胞核畸形。以前的研究表明，法尼基转移酶抑制剂(FTI)可以逆转这种细胞异常。我们测试了FTI(ABT-100)对Zmpste24缺陷小鼠的疗效，Zmpste24缺陷小鼠是一种早衰症小鼠模型。FTI处理的小鼠在20周大时显示出更好的体重、握力、骨骼完整性和存活率。这些结果表明，FTI可能对患有早衰症的人类有有益的影响。
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.