Huntingtons disease (HD) is an autosomal dominant progressive neurodegenerative disorder with onset generally in midlife. HD is characterized by chorea, dementia, and neuropsychiatric problems. The mutation lies in the expansion of a polymorphic CAG repeat resulting in greater than normal length of polyglutamines in the N-terminal end of the HD gene product (huntingtin) which is of unknown function. The lab has been successful in creating mouse models for HD that recapitulates features of behavioral abnormalities and neuropathological changes inherent in the human disease. Additional mouse models are being made for molecules that play a role in HD pathogenesis as well as in other CAG-repeat associated disorders. We are currently taking advantage of these models to elucidate the early molecular, biochemical and cellular events in the disease process; to identify modifying factors in the disease by way of protein-protein interaction and genetic screens; and to evaluate the usefulness of pharmacological agents and other therapeutic approaches towards the management and cure of the disease. - Huntington's disease, brain, neurodegeneration, animal models, therapeutics, CAG disease, neuronal loss, striatum, excitotoxicity
