Mitochondrial dysfunction and unfolded protein response in the pathogenesis of SCA3 in primary cell culture experiments

The spinocerebellar ataxia type 3 (SCA3), also known as Machado-Joseph disease (MJD), is an autosomal dominantly inherited neurodegenerative disorder caused by an expanded CAG repeat in the ataxin-3 gene. To consider the correlation between mitochondrial dysfunction and the pathogenesis of SCA3, we analysed mouse embryonic fibroblasts (MEF), which derived from SCA3 mutant mice, generated by the gene trap (gt) approach. Heterozygous (wt/gt) and homozygous (gt/gt) SCA3 mutant MEF cells were compared to wildtype controls. In vivo and in vitro studies in the SCA3 mutant mouse model revealed an effect of the unfolded…