Sustained effects of nonallele-specificHuntingtinsilencing
| العنوان: | Sustained effects of nonallele-specificHuntingtinsilencing |
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| المؤلفون: | Sandro Alves, Gwennaelle Auregan, Emmanuel Brouillet, Ruth Luthi-Carter, Raymonde Hassig, Valérie Drouet, Gilles Bonvento, Nicole Déglon, Noelle Dufour, Philippe Hantraye, Valérie Perrin |
| المصدر: | Annals of Neurology. 65:276-285 |
| بيانات النشر: | Wiley, 2009. |
| سنة النشر: | 2009 |
| مصطلحات موضوعية: | Male, Dopamine and cAMP-Regulated Phosphoprotein 32, congenital, hereditary, and neonatal diseases and abnormalities, Huntingtin, Nerve Tissue Proteins, Deoxyglucose, Biology, medicine.disease_cause, Mice, Exon, RNA interference, mental disorders, medicine, Animals, Humans, Gene silencing, RNA, Messenger, RNA, Small Interfering, Rats, Wistar, Nuclear protein, Cell Line, Transformed, Regulation of gene expression, Genetics, Huntingtin Protein, Mutation, Reverse Transcriptase Polymerase Chain Reaction, Neurodegeneration, Nuclear Proteins, Reproducibility of Results, Exons, medicine.disease, Corpus Striatum, Rats, nervous system diseases, Mice, Inbred C57BL, Succinate Dehydrogenase, Disease Models, Animal, Huntington Disease, Gene Expression Regulation, nervous system, Neurology, Doxycycline, Cancer research, Female, RNA Interference, Neurology (clinical) |
| الوصف: | Huntington's disease (HD) is a fatal autosomal dominant neurodegenerative disorder caused by a polyglutamine expansion in the huntingtin (htt) protein. No cure is available to date to alleviate neurodegeneration. Recent studies have demonstrated that RNA interference represents a promising approach for the treatment of autosomal dominant disorders. But whether an allele-specific silencing of mutant htt or a nonallele-specific silencing should be considered has not been addressed.We developed small hairpin RNA targeting mutant or wild-type htt transcripts, or both.We confirmed the therapeutic potential of sihtt administered with lentiviral vectors in rodent models of HD and showed that initiation of small interfering RNA treatment after the onset of HD symptoms is still efficacious and reduces the HD-like pathology. We then addressed the question of the impact of nonallele-specific silencing and demonstrated that silencing of endogenous htt to 25 to 35% in vivo is altering several pathways associated with known htt functions but is not inducing overt toxicity or increasing striatal vulnerability up to 9 months after treatment.These data indicate that the coincident silencing of the wild-type and mutant htt may be considered as a therapeutic tool for HD. |
| تدمد: | 1531-8249 0364-5134 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::abc11695e73d4fc709f4faa17a0c7f9cTest https://doi.org/10.1002/ana.21569Test |
| حقوق: | CLOSED |
| رقم الانضمام: | edsair.doi.dedup.....abc11695e73d4fc709f4faa17a0c7f9c |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 15318249 03645134 |
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