Fig. 1

Aggregation, transport and clearance of α-synuclein. a Concept of aggregation and spreading: After ribosomal translation of pathogenic α-synuclein (aSyn), monomers (1) form oligomers (2) and primary nucleation with formation of the first aggregate takes place. Subsequent steps are fibril elongation (3) and secondary nucleation with formation of further nuclei, e.g. by fibrils breaking (4). The aggregates are transported along the axonal projections, secreted and taken up by a neighboring cell (5). The aggregation of aSyn monomers is greatly enhanced by addition of even small quantities of aggregates, which serve as nuclei and replace the slow step of primary nucleation by the faster step of secondary nucleation. This process is called seeding (6). b Transport and autophagic clearance of aSyn: Aggregates are dynein-dependently transported to the perinuclear region to form aggresomes. Parts of the cytosol containing aggregates get engulfed by a membrane to form autophagosomes. Subsequently, Rab7 regulates the trafficking of autophagosomal and lysosomal vesicles and their fusion towards autolysosomes, followed by degradation of the vesicle content. There is also evidence for the secretion via exosomal release