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| Content Provider | PubMed Central |
|---|---|
| Author | Hockly, Emma Richon, Victoria M. Woodman, Benjamin Smith, Donna L. Zhou, Xianbo Rosa, Eddie Sathasivam, Kirupa Shabnam, Ghazi-noori Mahal, Amarbirpal Lowden, Philip A. S. Steffan, Joan S. Marsh, J. Lawrence Thompson, Leslie M. Lewis, Cathryn M. Marks, Paul A. Bates, Gillian P. |
| Copyright Year | 2003 |
| Abstract | 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. |
| Related Links | http://dx.doi.org/10.1073/pnas.0437870100 |
| Ending Page | 2046 |
| Page Count | 6 |
| Starting Page | 2041 |
| File Format | |
| ISSN | 00278424 |
| e-ISSN | 10916490 |
| Journal | Proceedings of the National Academy of Sciences of the United States of America |
| Issue Number | 4 |
| Volume Number | 100 |
| Language | English |
| Publisher | The National Academy of Sciences |
| Publisher Date | 2003-02-18 |
| Access Restriction | Open |
| Rights Holder | The National Academy of Sciences |
| Subject Keyword | General Research in Higher Education |
| Content Type | Text |
| Resource Type | Article |
| Subject | Multidisciplinary |
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