Huntington's disease: from gene to potential therapy

Huntington's disease (HD) is a progressive, late-onset neurodegenerative illness with autosomal dominant inheritance that affects one in 10 000 individuals in Western Europe. The disease is caused by a polyglutamine repeat expansion located in the N-terminal region of the huntingtin protein. The mutation is likely to act by a gain of function, but the molecular mechanisms by which it leads to neuronal dysfunction and cell death are not yet known. The normal function of huntingtin in cell metabolism is also unclear. There is no therapy for HD. Research on HD should help elucidate the pathogenetic mechanism of this illness in order to develop successful treatments to prevent or slow down symptoms. This article presents new results in HD research focusing on in vivo and in vitro model systems, potential molecular mechanisms of HD, and the development of therapeutic strategies.