Huntington’s Disease: Neurodegeneration

Huntington’s disease (HD) is an autosomal dominant disorder caused by an elongated CAG repeat in the huntingtin gene. Symptoms are not only dominated by progressive chorea but also include psychiatric signs and progressive dementia. Postmortem brains of late-stage patients show extensive atrophy of the striatum (caudate nucleus and putamen), cerebral cortex, and pallidum, with corresponding neuronal loss primarily in the striatum. The mutation causes profound neuronal dysfunction independent of, or prior to, neurodegeneration, suggesting that pathophysiological mechanisms of dysfunction may be more pertinent therapeutic targets than neurodegeneration itself. Drugs targeting many cellular processes have shown some efficacy in animal models, but no neuroprotective treatments are presently available for humans.