Polyglutamine spinocerebellar ataxias — from genes to potential treatments

Several of the spinocerebellar ataxias (SCAs) result from expansion of polyglutamine (polyQ)-encoding regions in different genes. Here, Orr and colleagues examine the clinical features of the the polyQ SCAs, and suggest that understanding the molecular and physiological mechanisms underlying polyQ SCAs can inform therapeutic strategies for these and other polyQ disorders. The dominantly inherited spinocerebellar ataxias (SCAs) are a large and diverse group of neurodegenerative diseases. The most prevalent SCAs (SCA1, SCA2, SCA3, SCA6 and SCA7) are caused by expansion of a glutamine-encoding CAG repeat in the affected gene. These SCAs represent a substantial portion of the polyglutamine neurodegenerative disorders and provide insight into this class of diseases as a whole. Recent years have seen considerable progress in deciphering the clinical, pathological, physiological and molecular aspects of the polyglutamine SCAs, with these advances establishing a solid base from which to pursue potential therapeutic approaches.