Degree
Master of Science
Program
Biochemistry
Supervisor
Dr. Gary Shaw
Abstract
Mutations in the gene encoding parkin (PARK2) result in familial early onset forms of Parkinson’s disease (PD) based on the loss of parkin’s E3 ubiquitin ligase function. Protein misfolding is a common molecular feature of most neurodegenerative diseases, including PD. To test whether parkin misfolding also plays a role in the more common spontaneous PD, we established and functionally characterized a parkin yeast model. We found that oxidative and protein folding stress, parkin point mutations and truncations, and parkin’s interaction with the PD-associated kinase PINK1 profoundly alter parkin’s subcellular localization and toxicity. Notably, these conditions also induce parkin fragmentation, degradation, and potentially misfolding, all of which may contribute to PD pathogenesis. Future research presents great potential to establish parkin misfolding as a promising new therapeutic target for PD.
Recommended Citation
McCarton, Alexander S., "Parkin Misfolding, Dysfunction, and Degradation in Parkinson's Disease" (2016). Electronic Thesis and Dissertation Repository. 3799.
https://ir.lib.uwo.ca/etd/3799