Advances in Huntington's disease: Implications for experimental therapeutics

The gene mutation causing Huntington's disease was identified in 1993 as an expanded trinucleotide repeat within the coding region for a 348-kd protein called huntingtin. The mechanism by which this cytosine-adenosine-guanosine repeat produces the progressive signs and symptoms of Huntington's disease remains uncertain, but recent advances have begun to provide insights into this process. Promising developments include transgenic mouse models of Huntington's disease with neuronal intranuclear inclusions, the identification of differential neuronal features which might account for the selective vulnerability of neurons seen in Huntington's disease and further evidence for the role of excitotoxicity and impaired mitochondrial energy production. These observations have suggested new therapeutic strategies, and have lent further support for experimental therapeutics aimed at improving mitochondrial function and reducing excitotoxic injury. (C) 1998 Lippincott-Raven Publishers.