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.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Animals, Genetically Modified
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Benzamides / chemistry*
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Benzamides / pharmacology
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Caenorhabditis elegans
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Cell Movement / drug effects*
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Green Fluorescent Proteins / genetics
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Green Fluorescent Proteins / metabolism
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Histone Deacetylase Inhibitors / chemical synthesis
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Histone Deacetylase Inhibitors / chemistry
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Histone Deacetylase Inhibitors / pharmacology*
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Muscle Cells / drug effects*
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Muscular Dystrophy, Oculopharyngeal
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Naphthols / chemistry*
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Naphthols / pharmacology
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Poly(A)-Binding Protein I / genetics
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Poly(A)-Binding Protein I / metabolism*
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Sirtuins / antagonists & inhibitors*
Substances
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Benzamides
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Histone Deacetylase Inhibitors
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Naphthols
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Poly(A)-Binding Protein I
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sirtinol
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Green Fluorescent Proteins
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Sirtuins