title: α-Synuclein fate: proteasome or autophagy?
abstract: The accumulation of α-synuclein is critical for the development of Parkinson disease (PD), and unraveling the mechanisms that regulate α-synuclein levels is key to understanding the pathophysiology of the disease. We recently found that USP9X deubiquitinates α-synuclein, and that this process determines the partition of α-synuclein between the proteasomal and autophagy pathways. By manipulating USP9X levels, we observed that monoubiquitinated α-synuclein is degraded by the proteasome, whereas deubiquitination of α-synuclein favors its degradation by autophagy. As USP9X levels and activity are decreased in α-synucleinopathy brains, USP9X may now represent a novel target for PD.
authors.affiliation: Department of Pharmacology, The B. Rappaport Faculty of Medicine and Institute of Medical Research, Technion-Israel Institute of Technology, Haifa, Israel. simone@tx.technion.ac.il
authors.forename: Simone
authors.initials: S
authors.lastname: Engelender
mesh_terms: D001343:Autophagy; D006801:Humans; D008954:Models, Biological; D010300:Parkinson Disease / Q000378:metabolism / Q000473:pathology; D046988:Proteasome Endopeptidase Complex / Q000378:metabolism*; D015398:Signal Transduction; D043222:Ubiquitin Thiolesterase / Q000378:metabolism; D054875:Ubiquitination; D051844:alpha-Synuclein / Q000378:metabolism*
chemical_list: C506234:USP9X protein, human; D051844:alpha-Synuclein; D043222:Ubiquitin Thiolesterase; D046988:Proteasome Endopeptidase Complex