Suberoylanilide hydroxamic acid, a histone deacetylase inhibitor, ameliorates motor deficits in a mouse model of Huntington's disease
| Autor: | J.L. Marsh, Shabnam Ghazi-Noori, Gillian P. Bates, Kirupa Sathasivam, Victoria M. Richon, Leslie M. Thompson, Xianbo Zhou, Donna L. Smith, Amarbirpal Mahal, Cathryn M. Lewis, Paul A. Marks, Emma Hockly, Philip A. S. Lowden, Joan S. Steffan, E. Rosa, Benjamin Woodman |
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| Jazyk: | angličtina |
| Rok vydání: | 2003 |
| Předmět: |
medicine.drug_class
Mice Transgenic Blood–brain barrier Hydroxamic Acids Histones Mice Huntington's disease medicine Animals Transgenes Enzyme Inhibitors DNA Primers Vorinostat Multidisciplinary Movement Disorders biology Base Sequence Reverse Transcriptase Polymerase Chain Reaction Neurodegeneration Histone deacetylase inhibitor Brain Acetylation Biological Sciences medicine.disease Molecular biology Histone Deacetylase Inhibitors Disease Models Animal Histone medicine.anatomical_structure Huntington Disease Blood-Brain Barrier biology.protein Cancer research Female Histone deacetylase Trinucleotide repeat expansion |
| Popis: | Huntington's disease (HD) is an inherited, progressive neurological disorder that is caused by a CAG/polyglutamine repeat expansion and for which there is no effective therapy. Recent evidence indicates that transcriptional dysregulation may contribute to the molecular pathogenesis of this disease. Supporting this view, administration of histone deacetylase (HDAC) inhibitors has been shown to rescue lethality and photoreceptor neurodegeneration in a Drosophila model of polyglutamine disease. To further explore the therapeutic potential of HDAC inhibitors, we have conducted preclinical trials with suberoylanilide hydroxamic acid (SAHA), a potent HDAC inhibitor, in the R6/2 HD mouse model. We show that SAHA crosses the blood–brain barrier and increases histone acetylation in the brain. We found that SAHA could be administered orally in drinking water when complexed with cyclodextrins. SAHA dramatically improved the motor impairment in R6/2 mice, clearly validating the pursuit of this class of compounds as HD therapeutics. |
| Databáze: | OpenAIRE |
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