Dissecting the mechanism of neuronal demise in Huntington disease (HD) has had its share of twists and turns. It took a decade to go from marker1 to gene,2 and now, after another decade, the details are beginning to come together. Three papers published in 2001 focus on two key roles for the pathological form of huntingtin protein--interfering with transcription3,4 and plugging up proteasomes, the cellular trash compactors for misfolded proteins.5 While different, these hypotheses are not mutually exclusive, and may point to multiple effects that inevitably cause the devastating symptoms of HD.
In the late 1800s, Long Island physician George Huntington lent his name to this disorder, which is characterized by uncontrollable, dancelike movements and personality changes.6 After a long illness, individuals with HD die from complications such as choking or infection. The genetic marker discovered in 1983 had the uninspiring name G8 and the gene discovered 10 years later ...
