Human molecular genetics
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Human molecular genetics · Feb 2019
Ubiquitin specific protease-13 independently regulates parkin ubiquitination and alpha-synuclein clearance in alpha-synucleinopathies.
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. ⋯ 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.