Of molecular interactions, mice and mechanisms: new insights into Huntington's disease

Huntington's disease is caused by expansion of a CAG trinucleotide beyond 35 repeats within the coding region of a novel gene. Recently, new insights into the relationship between CAG expansion in the HD gene and pathological mechanisms have emerged. These include a more precise understanding of the relationship between CAG repeat length and age of onset, progress in transgenic and excitotoxic animal models, identification of a novel huntingtin-interacting protein, and intriguing connections between huntingtin and the apoptotic machinery. We have combined many of these new findings into a model that suggests mechanisms and predicts outcomes by which the pathogenesis of Huntington's disease may be initiated. The development of appropriate in-vitro and animal models for Huntington's disease will allow the Validity of this model to be tested.