| Autor: |
Evers MM; Center for Human and Clinical Genetics, Leiden University Medical Center, Leiden, The Netherlands., Pepers BA, van Deutekom JC, Mulders SA, den Dunnen JT, Aartsma-Rus A, van Ommen GJ, van Roon-Mom WM |
| Jazyk: |
angličtina |
| Zdroj: |
PloS one [PLoS One] 2011; Vol. 6 (9), pp. e24308. Date of Electronic Publication: 2011 Sep 01. |
| DOI: |
10.1371/journal.pone.0024308 |
| Abstrakt: |
To date there are 9 known diseases caused by an expanded polyglutamine repeat, with the most prevalent being Huntington's disease. Huntington's disease is a progressive autosomal dominant neurodegenerative disorder for which currently no therapy is available. It is caused by a CAG repeat expansion in the HTT gene, which results in an expansion of a glutamine stretch at the N-terminal end of the huntingtin protein. This polyglutamine expansion plays a central role in the disease and results in the accumulation of cytoplasmic and nuclear aggregates. Here, we make use of modified 2'-O-methyl phosphorothioate (CUG)n triplet-repeat antisense oligonucleotides to effectively reduce mutant huntingtin transcript and protein levels in patient-derived Huntington's disease fibroblasts and lymphoblasts. The most effective antisense oligonucleotide, (CUG)(7), also reduced mutant ataxin-1 and ataxin-3 mRNA levels in spinocerebellar ataxia 1 and 3, respectively, and atrophin-1 in dentatorubral-pallidoluysian atrophy patient derived fibroblasts. This antisense oligonucleotide is not only a promising therapeutic tool to reduce mutant huntingtin levels in Huntington's disease but our results in spinocerebellar ataxia and dentatorubral-pallidoluysian atrophy cells suggest that this could also be applicable to other polyglutamine expansion disorders as well. |
| Databáze: |
MEDLINE |
| Externí odkaz: |
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