title: Lithium carbonate and coenzyme Q10 reduce cell death in a cell model of Machado-Joseph disease.
abstract: 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.
authors.affiliation: Departamento de Genética Médica, Faculdade de Ciências Médicas, Universidade Estadual de Campinas, Campinas, SP, Brasil.
authors.forename: C M
authors.initials: CM
authors.lastname: Lopes-Ramos
authors.affiliation: Departamento de Biologia, Faculdade de Filosofia, Ciências e Letras de Ribeirão Preto, Universidade de São Paulo, Ribeirão Preto, SP, Brasil.
authors.forename: T C
authors.initials: TC
authors.lastname: Pereira
authors.affiliation: Departamento de Genética Médica, Faculdade de Ciências Médicas, Universidade Estadual de Campinas, Campinas, SP, Brasil.
authors.forename: D B
authors.initials: DB
authors.lastname: Dogini
authors.affiliation: Centro Multidisciplinar para Investigação Biológica, Universidade Estadual de Campinas, Campinas, SP, Brasil.
authors.forename: R
authors.initials: R
authors.lastname: Gilioli
authors.affiliation: Departamento de Genética Médica, Faculdade de Ciências Médicas, Universidade Estadual de Campinas, Campinas, SP, Brasil.
authors.forename: I
authors.initials: I
authors.lastname: Lopes-Cendes
mesh_terms: D000067699:Ataxin-3 / Q000187:drug effects*; D016923:Cell Death / Q000187:drug effects*; D002454:Cell Differentiation / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D006801:Humans; D016651:Lithium Carbonate / Q000494:pharmacology*; D017827:Machado-Joseph Disease / Q000188:drug therapy; D012097:Repressor Proteins / Q000187:drug effects*; D014451:Ubiquinone / Q000031:analogs & derivatives* / Q000494:pharmacology
chemical_list: D012097:Repressor Proteins; D014451:Ubiquinone; D016651:Lithium Carbonate; C092341:ATXN3 protein, human; D000067699:Ataxin-3; C024989:coenzyme Q10