OF MOLECULAR-INTERACTIONS, MICE AND MECHANISMS - NEW INSIGHTS INTO HUNTINGTONS-DISEASE

Huntington's disease is caused by expansion of a CAG trinucleotide bey ond 35 repeats within the coding region of a novel gene. Recently, new insights into the relationship between CAG expansion in the HD gene a nd 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, identifi cation of a novel huntingtin-interacting protein, and intriguing conne ctions between huntingtin and the apoptotic machinery. We have combine d many of these new findings into a model that suggests mechanisms and predicts outcomes by which the pathogenesis of Huntington's disease m ay be initiated. The development of appropriate in-vitro and animal mo dels for Huntington's disease will allow the Validity of this model to be tested.