Ai Yamamoto, PhD
Research Laboratories for Parkinson's Disease
» Division of Parkinson's Disease and Other Movement Disorders
» Department of Neurology
The ability of any cell to function properly relies heavily in its ability to traffic proteins to its correct destination. This is especially true for a large, highly polarized, post-mitotic cell such as a neuron. From maintaining proteins at the cell membrane and permit proper signaling, to sequestering and moving proteins away for their ultimate destruction, knowing when and how proteins are selected and targeted is as critical as understanding the function of the proteins themselves. We therefore use cellular, biochemical and genetic methods to determine how proteins are targeted for two events: degradation and endocytosis. To interrogate these pathways, we examine them in the context of the neurological disorders Huntington's disease (HD) and Parkinson's disease (PD) to determine whether they can modify disease pathogenesis. Our current effort focuses on a recurrent observation in neurodegeneration- the accumulation and aggregation of mutant proteins. It has been shown that in diseases such as HD, elimination of mutant protein accumulation not only halts symptomatic progression but reverses the disease. The question remains, however, how do we selectively eliminate the mutant protein, and what form of the protein should we eliminate? Using cellular and in vivo models, our goal is to answer this and other related questions, ultimately to test our original hypothesis that selective elimination of aggregated proteins is required to ameliorate HD.