Lithium chloride therapy fails to improve motor function in a transgenic mouse model of Machado-Joseph disease

• Autor(a) principal: Silva, Sara Duarte
• Data de Publicação: 2014
• Outros Autores: Carvalho, Andreia Neves, Cunha, Carina Soares, Castro, Andreia Cristiana Teixeira de, Oliveira, Pedro, Fernandes, Anabela Silva, Maciel, P.
• Tipo de documento: Artigo
• Idioma: eng
• Título da fonte: Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
• Texto Completo: http://hdl.handle.net/1822/33268
• topic: Autophagy; Lithium; Polyglutamine; Spinocerebellar ataxia; Therapy; Triplet repeats; Science & Technology

The accumulation of misfolded proteins in neurons, leading to the formation of cytoplasmic and nuclear aggregates, is a common theme in age-related neurodegenerative diseases, possibly due to disturbances of the proteostasis and insufficient activity of cellular protein clearance pathways. Lithium is a well-known autophagy inducer that exerts neuroprotective effects in different conditions and has been proposed as a promising therapeutic agent for several neurodegenerative diseases. We tested the efficacy of chronic lithium 10.4 mg/kg) treatment in a transgenic mouse model of Machado-Joseph disease, an inherited neurodegenerative disease, caused by an expansion of a polyglutamine tract within the protein ataxin-3. A battery of behavioral tests was used to assess disease progression. In spite of activating autophagy, as suggested by the increased levels of Beclin-1, Atg7, and LC3II, and a reduction in the p62 protein levels, lithium administration showed no overall beneficial effects in this model concerning motor performance, showing a positive impact only in the reduction of tremors at 24 weeks of age. Our results do not support lithiumchronic treatment as a promising strategy for the treatment of Machado-Joseph disease (MJD).