title: Protein farnesyltransferase inhibitors and progeria.
abstract: Genetic mutations that lead to an accumulation of farnesyl-prelamin A cause progeroid syndromes, including Hutchinson-Gilford progeria syndrome. It seemed possible that the farnesylated form of prelamin A might be toxic to mammalian cells, accounting for all the disease phenotypes that are characteristic of progeria. This concept led to the hypothesis that protein farnesyltransferase inhibitors (FTIs) might ameliorate the disease phenotypes of progeria in mouse models. Thus far, two different mouse models of progeria have been examined. In both models, FTIs improved progeria-like disease phenotypes. Here, prelamin A post-translational processing is discussed and several mutations underlying human progeroid syndromes are described. In addition, recent data showing that FTIs ameliorate disease phenotypes in a pair of mouse models of progeria are discussed.
authors.affiliation: Department of Medicine, Division of Cardiology, David Geffen School of Medicine, University of California, Los Angeles, CA 90095, USA.
authors.forename: Margarita
authors.initials: M
authors.lastname: Meta
authors.forename: Shao H
authors.initials: SH
authors.lastname: Yang
authors.forename: Martin O
authors.initials: MO
authors.lastname: Bergo
authors.forename: Loren G
authors.initials: LG
authors.lastname: Fong
authors.forename: Stephen G
authors.initials: SG
authors.lastname: Young
mesh_terms: D019883:Alkyl and Aryl Transferases / Q000037:antagonists & inhibitors* / Q000235:genetics; D000818:Animals; D004195:Disease Models, Animal; D004791:Enzyme Inhibitors / Q000494:pharmacology / Q000627:therapeutic use*; D006801:Humans; D034904:Lamin Type A / Q000096:biosynthesis; D008565:Membrane Proteins / Q000378:metabolism; D008666:Metalloendopeptidases / Q000378:metabolism; D051379:Mice; D011371:Progeria / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism; D011499:Protein Processing, Post-Translational
chemical_list: D004791:Enzyme Inhibitors; D034904:Lamin Type A; D008565:Membrane Proteins; D019883:Alkyl and Aryl Transferases; C064911:p21(ras) farnesyl-protein transferase; D008666:Metalloendopeptidases; C491250:Zmpste24 protein, mouse