Polyglutamine expansions: mechanisms of disease

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The spinocerebellar ataxias (SCAs) are a complex group of often fatal neurodegenerative disorders. Five of the known autosomal dominant loci (SCA1–3, SCA6 and SCA7) are characterized by expanded CAG repeats that are translated into expanded polyglutamine tracts. It has previously been shown in SCA3 that polyglutamine expansion results in an altered, presumably misfolded, protein that forms intranuclear aggregates called nuclear inclusions (NIs). As NIs are ubiquinated, it might be that the ubiquitin–proteasome pathway is involved in the pathogenesis of this disorder.