Our major research goal is to identify the processes underlying the mechanism of neurodegeneration in Parkinson's disease (PD) and related disorders. Considerable evidence suggests the neuronal damage that occurs in neurodegenerative disorders may be caused by the accumulation of toxic, abnormal, aggregation-prone proteins resulting in impairment in the ubiquitin proteasome system (UPS). The ubiquitin-proteasome system (UPS) is the principal means by which short-lived and abnormal/misassembled proteins are degraded in eukaryotic cells. Mutations in enzymes involved in ubiquitination have been associated with familial forms of PD, including loss of function mutations in parkin and ubiquitin c-terminal hydryloase suggesting a possible dysregulation of protein mishandling or UPS activity as a potential causal role in PD. Our studies are geared toward unraveling the role of UPS and chaperones and devising therapeutic strategies to hamper the processes that cause neuronal death.