Sci. Aging Knowl. Environ., 8 March 2006
A Protein Farnesyltransferase Inhibitor Ameliorates Disease in a Mouse Model of Progeria
Loren G. Fong, David Frost, Margarita Meta, Xin Qiao, Shao H. Yang, Catherine Coffinier, and Stephen G. Younghttp://sageke.sciencemag.org/cgi/content/abstract/2006/6/or7
Abstract: Science 16 February 2006 (10.1126/science.1124875) (Science Express Report)
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. Here, we test 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.
Science of Aging Knowledge Environment. ISSN 1539-6150