| First Author | Liu X | Year | 2019 |
| Journal | Hum Mol Genet | Volume | 28 |
| Issue | 4 | Pages | 548-560 |
| PubMed ID | 30329047 | Mgi Jnum | J:271093 |
| Mgi Id | MGI:6279119 | Doi | 10.1093/hmg/ddy365 |
| Citation | Liu X, et al. (2019) Ubiquitin specific protease-13 independently regulates parkin ubiquitination and alpha-synuclein clearance in alpha-synucleinopathies. Hum Mol Genet 28(4):548-560 |
| abstractText | Ubiquitin specific proteases (USPs) are de-ubiquitinases (DUBs) that control protein ubiquitination cycle. The role of DUBs is poorly understood in neurodegenerative diseases. We found that USP13 is overexpressed in post-mortem Parkinson's disease (PD) brains. We investigated whether changes in USP13 levels can affect two molecules, parkin and alpha-synuclein, that are implicated in PD pathogenesis. Parkin is an E3 ubiquitin ligase that is regulated by ubiquitination and targets certain proteins for degradation, and alpha-synuclein may be ubiquitinated and recycled in the normal brain. We found that USP13 independently regulates parkin and alpha-synuclein ubiquitination in models of alpha-synucleinopathies. USP13 shRNA knockdown increases alpha-synuclein ubiquitination and clearance, in a parkin-independent manner. Furthermore, USP13 overexpression counteracts the effects of a tyrosine kinase inhibitor, Nilotinib, while USP13 knockdown facilitates Nilotinib effects on alpha-synculein clearance, suggesting that alpha-synuclein ubiquitnation is important for its clearance. These studies provide novel evidence of USP13 effects on parkin and alpha-synuclein metabolism and suggest that USP13 is a potential therapeutic target in the alpha-synucleinopathies. |
