Figure 5
From: Degradation of misfolded proteins in neurodegenerative diseases: therapeutic targets and strategies
The degradation of α-synuclein by cellular protein quality control. Wild-type and mutant α-synuclein can be targeted by the ubiquitination-dependent UPS (A) and possibly in a manner independent from Ub (B) as well. Monomeric α-synuclein can also be targeted by the CMA (C). By contrast, macroautophagy can degrade monomeric and oligomeric α-synuclein as well as its aggregates (D). Intracellular α-synuclein can also be cleaved by endopeptidases, such as calpains (E) and neurosin (F). Extracellular α-synuclein can be cleaved by neurosin (G) and metalloproteinases (H). The resulting proteolytic cleavage products are thought to contribute to the cytotoxicity of α-synuclein. Modified from Xilouri et al.228
