Huntington’s disease: Pathogenic mechanisms and therapeutic targets

Abstract

Huntington’s disease (HD) is a tandem repeat disorder involving neurodegeneration and a complex combination of symptoms. These include psychiatric symptoms, cognitive deficits culminating in dementia, and the movement disorder epitomised by motor signs such as chorea. HD is caused by a CAG repeat expansion encoding an extended tract of the amino acid glutamine in the huntingtin protein. This polyglutamine expansion appears to induce a ‘change of function’, possibly a ‘gain of function’, in the huntingtin protein, which leads to various molecular and cellular cascades of pathogenesis. In the current review, we will briefly describe these broader aspects of HD pathogenesis, but will then focus..