Utilize este identificador para referenciar este registo:
https://hdl.handle.net/10316/27705
Título: | RNA Interference Mitigates Motor and Neuropathological Deficits in a Cerebellar Mouse Model of Machado-Joseph Disease | Autor: | Nóbrega, Clévio Nascimento-Ferreira, Isabel Onofre, Isabel Albuquerque, David Déglon, Nicole Almeida, Luís Pereira de |
Data: | 21-Ago-2014 | Editora: | PLOS | Citação: | NÓBREGA, Clévio [et. al] - RNA Interference Mitigates Motor and Neuropathological Deficits in a Cerebellar Mouse Model of Machado-Joseph Disease. "PLOS one". ISSN 1932-6203. Vol. 9 Nº. 8 (2014) p. e100086 | Título da revista, periódico, livro ou evento: | PLOS one | Volume: | 9 | Número: | 8 | Resumo: | Machado-Joseph disease or Spinocerebellar ataxia type 3 is a progressive fatal neurodegenerative disorder caused by the polyglutamine-expanded protein ataxin-3. Recent studies demonstrate that RNA interference is a promising approach for the treatment of Machado-Joseph disease. However, whether gene silencing at an early time-point is able to prevent the appearance of motor behavior deficits typical of the disease when initiated before onset of the disease had not been explored. Here, using a lentiviral-mediated allele-specific silencing of mutant ataxin-3 in an early pre-symptomatic cerebellar mouse model of Machado-Joseph disease we show that this strategy hampers the development of the motor and neuropathological phenotypic characteristics of the disease. At the histological level, the RNA-specific silencing of mutant ataxin-3 decreased formation of mutant ataxin-3 aggregates, preserved Purkinje cell morphology and expression of neuronal markers while reducing cell death. Importantly, gene silencing prevented the development of impairments in balance, motor coordination, gait and hyperactivity observed in control mice. These data support the therapeutic potential of RNA interference for Machado-Joseph disease and constitute a proof of principle of the beneficial effects of early allelespecific silencing for therapy of this disease. | URI: | https://hdl.handle.net/10316/27705 | ISSN: | 1932-6203 | DOI: | 10.1371/journal.pone.0100086 | Direitos: | openAccess |
Aparece nas coleções: | FFUC- Artigos em Revistas Internacionais I&D CNC - Artigos em Revistas Internacionais |
Ficheiros deste registo:
Ficheiro | Descrição | Tamanho | Formato | |
---|---|---|---|---|
RNA Interference Mitigates.pdf | 3.01 MB | Adobe PDF | Ver/Abrir |
Citações SCOPUSTM
34
Visto em 14/out/2024
Citações WEB OF SCIENCETM
5
32
Visto em 2/out/2024
Visualizações de página 10
1.057
Visto em 8/out/2024
Downloads 50
519
Visto em 8/out/2024
Google ScholarTM
Verificar
Altmetric
Altmetric
Todos os registos no repositório estão protegidos por leis de copyright, com todos os direitos reservados.