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https://hdl.handle.net/10316/106332
Título: | Trehalose alleviates the phenotype of Machado-Joseph disease mouse models | Autor: | Santana, Magda M. Paixão, Susana Cunha-Santos, Janete Silva, Teresa Pereira Trevino-Garcia, Allyson Gaspar, Laetitia da Silva Nóbrega, Clévio Nobre, Rui J. Cavadas, Cláudia Greif, Hagar Almeida, Luís Pereira de |
Palavras-chave: | Machado-Joseph disease; Spinocerebellar ataxia type 3; Polyglutamine disorder; Trehalose; Autophagy | Data: | 9-Abr-2020 | Editora: | Springer Nature | Título da revista, periódico, livro ou evento: | Journal of Translational Medicine | Volume: | 18 | Número: | 1 | Resumo: | Background: Machado–Joseph disease (MJD), also known as spinocerebellar ataxia type 3, is the most common of the dominantly inherited ataxias worldwide and is characterized by mutant ataxin-3 aggregation and neuronal degeneration. There is no treatment available to block or delay disease progression. In this work we investigated whether trehalose, a natural occurring disaccharide widely used in food and cosmetic industry, would rescue biochemical, behavioral and neuropathological features of an in vitro and of a severe MJD transgenic mouse model. Methods: Two MJD animal models, a lentiviral based and a transgenic model, were orally treated with 2% trehalose solution for a period of 4 and 30 weeks, respectively. Motor behavior (rotarod, grip strength and footprint patterns) was evaluated at different time points and neuropathological features were evaluated upon in-life phase termination. Results: Trehalose-treated MJD mice equilibrated for a longer time in the rotarod apparatus and exhibited an improvement of ataxic gait in footprint analysis. Trehalose-mediated improvements in motor behaviour were associated with a reduction of the MJD-associated neuropathology, as MJD transgenic mice treated with trehalose presented preservation of cerebellar layers thickness and a decrease in the size of ataxin-3 aggregates in Purkinje cells. In agreement, an improvement of neuropathological features was also observed in the full length lentiviral-based mouse model of MJD submitted to 2% trehalose treatment. Conclusions: The present study suggests trehalose as a safety pharmacological strategy to counteract MJD-associated behavioural and neuropathological impairments. | URI: | https://hdl.handle.net/10316/106332 | ISSN: | 1479-5876 | DOI: | 10.1186/s12967-020-02302-2 | Direitos: | openAccess |
Aparece nas coleções: | I&D CNC - Artigos em Revistas Internacionais I&D CIBB - Artigos em Revistas Internacionais IIIUC - Artigos em Revistas Internacionais FFUC- Artigos em Revistas Internacionais |
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Ficheiro | Descrição | Tamanho | Formato | |
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Trehalose-alleviates-the-phenotype-of-MachadoJoseph-disease-mouse-modelsJournal-of-Translational-Medicine.pdf | 5.75 MB | Adobe PDF | Ver/Abrir |
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