Deciphering and Exploiting the Neuroprotective Activity of Parkin
Parkin Biology, 2013
Objective/Rationale: † † † † † ††
Mutations in the Parkin gene are responsible for parkinsonism, and there is evidence that Parkin is inactivated in sporadic (cause unknown) Parkinson's disease, suggesting an important role in the disease pathogenesis. The Parkin enzyme has wide-reaching neuroprotective activity, preventing cell death in various stress conditions. The goal of this project is to understand how Parkin mediates neuroprotection and how this activity can be exploited for novel therapeutic strategies.
Researchers recently observed that under cellular stress Parkin is recruited to the protein group LUBAC, the linear ubiquitin chain assemby complex, to activate NF-kappa B signaling, which is a major pro-survival pathway. By using several cellular models of Parkin deficiency, these investigators will analyze whether Parkin has an effect on LUBAC composition, modification and/or subcellular localization. In a next step they will address the question of how the neuroprotective activity of Parkin is regulated.
Relevance to Diagnosis/Treatment of Parkinsonís Disease: † † † † † † † † † ††
This project is focused on the analysis of a key pro-survival pathway that is activated by Parkin under stress conditions to maintain neuronal integrity. Researchers could use their findings as the basis for development of pharmacological interventions that could protect the neurons that degenerate in Parkinsonís disease.
Anticipated Outcome: † † † † †
The investigators hope to provide insights into the mechanism underlying the neuroprotective activity of Parkin that ultimately lead to the identification of cellular targets amenable to novel neuroprotective and therapeutic strategies.
Professor at Ruhr University Bochum
Location: Bochum, Germany