Crystal Structure Determination of a Key Processing Enzyme in Huntington’s Disease

Huntington’s disease (HD) is a neurodegenerative disorder caused by mutation of a single gene. The mutation is dominantly inherited with the disease affecting successive generations of afflicted families. HD has its onset usually in midlife, starting with a motor disorder such as chorea or the inability to sustain voluntary movements. The disease progresses with behavioural and cognitive symptoms, often manifested as delusional behaviour, poor concentration, apathy, depression, dementia, and ultimately premature death. Although to date there is no cure to the disease, discovery of the mutant huntingtin gene (mHtt) in 1993 has enabled significant progress to the understanding of the underlying disease mechanism. Studies aimed at developing a therapy are currently underway.