Genetic and molecular aspects of spinocerebellar ataxias

Viktor Honti¹, László Vécsei^1,2

¹Department of Neurology, Albert Szent-Györgyi Medical and Pharmaceutical Center, University of Szeged, Szeged, Hungary; ²Neurology Research Group of the Hungarian Academy of Sciences and University of Szeged, Szeged, Hungary

Abstract: The group of spinocerebellar ataxias (SCAs) includes more than 20 subgroups based only on genetic research. The “ataxia genes” are autosomal; the “disease-alleles” are dominant, and many of them, but not all, encode a protein with an abnormally long polyglutamine domain. In DNA, this domain can be detected as an elongated CAG repeat region, which is the basis of genetic diagnostics. The polyglutamine tails often tend to  aggregate and form inclusions. In some cases, protein–protein interactions are the key to understanding the disease. Protein partners of ataxia proteins include phosphatases and components of chromatin and the transcriptional machinery. To date, investigation of spinocerebellar ataxias involves population genetics, molecular methods, and studying model organisms. However, there is still no efficient therapy for patients. Here, we review the genetic and molecular data gained on spinocerebellar ataxias.

Keywords: ataxia, repeat, polyglutamine, autosomal, dominant