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(Referência obtida automaticamente do Web of Science, por meio da informação sobre o financiamento pela FAPESP e o número do processo correspondente, incluída na publicação pelos autores.)

Lithium carbonate and coenzyme Q10 reduce cell death in a cell model of Machado-Joseph disease

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Autor(es):
Lopes-Ramos, C. M. ; Pereira, T. C. ; Dogini, D. B. ; Gilioli, R. ; Lopes-Cendes, I.
Número total de Autores: 5
Tipo de documento: Artigo Científico
Fonte: Brazilian Journal of Medical and Biological Research; v. 49, n. 12 2016.
Citações Web of Science: 2
Resumo

Machado-Joseph disease (MJD) or spinocerebellar ataxia type 3 (SCA3) is an autosomal dominant neurodegenerative disorder caused by expansion of the polyglutamine domain of the ataxin-3 (ATX3) protein. MJD/SCA3 is the most frequent autosomal dominant ataxia in many countries. The mechanism underlying MJD/SCA3 is thought to be mainly related to protein misfolding and aggregation leading to neuronal dysfunction followed by cell death. Currently, there are no effective treatments for patients with MJD/SCA3. Here, we report on the potential use of lithium carbonate and coenzyme Q10 to reduce cell death caused by the expanded ATX3 in cell culture. Cell viability and apoptosis were evaluated by MTT assay and by flow cytometry after staining with annexin V-FITC/propidium iodide. Treatment with lithium carbonate and coenzyme Q10 led to a significant increase in viability of cells expressing expanded ATX3 (Q84). In addition, we found that the increase in cell viability resulted from a significant reduction in the proportion of apoptotic cells. Furthermore, there was a significant change in the expanded ATX3 monomer/aggregate ratio after lithium carbonate and coenzyme Q10 treatment, with an increase in the monomer fraction and decrease in aggregates. The safety and tolerance of both drugs are well established; thus, our results indicate that lithium carbonate and coenzyme Q10 are good candidates for further in vivo therapeutic trials. (AU)

Processo FAPESP: 07/57559-9 - Construção e avaliação de um modelo in vitro dos efeitos citotóxicos da ataxina-3 expandida e teste de compostos que possam reverter a formação de agregados intracelulares e seus efeitos citopáticos
Beneficiário:Camila Miranda Lopes Ramos
Linha de fomento: Bolsas no Brasil - Mestrado
Processo FAPESP: 13/07559-3 - Instituto Brasileiro de Neurociência e Neurotecnologia - BRAINN
Beneficiário:Fernando Cendes
Linha de fomento: Auxílio à Pesquisa - Centros de Pesquisa, Inovação e Difusão - CEPIDs