Figure 1.

The routes for α-synuclein (α-syn) clearance. α-Syn exists as a soluble monomer that can undergo misfolding into toxic species, dimers and intermediate oligomers, which can further form superfibriliar aggregates. The clearance of different α-syn species occurs via two main proteolytic systems, ubiquitin-proteasome system (UPS) and the lysosome-mediated degradation (particularly chaperone-mediated autophagy (CMA) and macroautophagy (referred as autophagy)). UPS and CMA are the main degradation routes of soluble wild type α-syn, while autophagy is the preferred clearance pathway for intermediate oligomers or mutant α-syn forms. α-Syn levels, mutations and post-translational modifications, impact on the proteolytic systems function leading to their collapse. Aging is also a factor associated with the impairment of the proteolytic systems function, which predispose the cells to the accumulation of α-syn toxic species. See the text for details.