Gonda 2309 695 Charles E. Young Dr. South Los Angeles CA 90095-1761 USA
PhD Biology, California Institute of Technology, Pasadena, CA
BA Biology (Concentrations: Molecular and Cell / Neurobiology and Behavior) 2006, Cornell University, Ithaca, NY
Investigation of PSA as a potential drug target to enhance tau degradation.
Tauopathies are a group of neurodegenerative diseases that are caused by hyperphosphorylation and subsequent accumulation of the protein tau. Here tau or aggregates of tau in neurons lead to dysfunction of these neurons and ultimately to cell death. This is manifested as dementia or movement disorders, depending on which region of the brain is affected. Currently, no treatments exists to slow progression of these diseases, therefore identifying new therapeutic targets is of immediate relevance. Puromycin-sensitive aminopeptidase (PSA), an enzyme recently identified by our lab as neuroprotective using a functional genomic approach in a mouse model of tauopathy (P301L), has been shown to reduce the levels of tau (Karsten et al., 2006). As tau reduction has been shown to block disease in both mouse and Drosophila models of tauopathy, PSA could be an important new therapeutic target for tauopathies. Therefore, we aim to further investigate the mechanisms by which PSA reduces tau, whether this degradation is affected by modifications of tau and if we can find small molecules that can increase the activity of PSA and thereby slow, or even reverse, disease progression.
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