title: Characterization of sirtuin inhibitors in nematodes expressing a muscular dystrophy protein reveals muscle cell and behavioral protection by specific sirtinol analogues.
abstract: In oculopharyngeal muscular dystrophy (OPMD), a disease caused by polyalanine expansion in the nuclear protein PABPN1, the genetic inhibition of sirtuins and treatment with sirtuin inhibitors protect from mutant PABPN1 toxicity in transgenic nematodes. Here, we tested the SIRT1/2 inhibitors 1-12, bearing different degrees of inhibition, for protection against mutant PABPN1 toxicity in Caenorhabditis elegans. Compounds 2, 4, and 11 were the most efficient, revealing a potential therapeutic application for muscle cell protection in OPMD.
authors.affiliation: INSERM, Laboratory of Neuronal Cell Biology and Pathology, Center for Psychiatry and Neurosciences U894, Paris, France.
authors.forename: Matthieu Y
authors.initials: MY
authors.lastname: Pasco
authors.forename: Dante
authors.initials: D
authors.lastname: Rotili
authors.forename: Lucia
authors.initials: L
authors.lastname: Altucci
authors.forename: Francesca
authors.initials: F
authors.lastname: Farina
authors.forename: Guy A
authors.initials: GA
authors.lastname: Rouleau
authors.forename: Antonello
authors.initials: A
authors.lastname: Mai
authors.forename: Christian
authors.initials: C
authors.lastname: Néri
mesh_terms: D000818:Animals; D030801:Animals, Genetically Modified; D001549:Benzamides / Q000737:chemistry* / Q000494:pharmacology; D017173:Caenorhabditis elegans; D002465:Cell Movement / Q000187:drug effects*; D049452:Green Fluorescent Proteins / Q000235:genetics / Q000378:metabolism; D056572:Histone Deacetylase Inhibitors / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D032342:Muscle Cells / Q000187:drug effects*; D039141:Muscular Dystrophy, Oculopharyngeal; D009284:Naphthols / Q000737:chemistry* / Q000494:pharmacology; D039122:Poly(A)-Binding Protein I / Q000235:genetics / Q000378:metabolism*; D037761:Sirtuins / Q000037:antagonists & inhibitors*
chemical_list: D001549:Benzamides; D056572:Histone Deacetylase Inhibitors; D009284:Naphthols; D039122:Poly(A)-Binding Protein I; C439060:sirtinol; D049452:Green Fluorescent Proteins; D037761:Sirtuins