Fig. 9

Model for the proposed mechanism of aSyn internalization and interaction with the membrane and trafficking machinery. After interacting with the plasma membrane, aSyn monomers are internalized through the endocytic pathway. Rab4A plays an important role in the sorting of aSyn and on the transport from/to the plasma membrane. aSyn is then found in the early endosome and, it is possible that during the progress from early to late endosome, due to acidification of the environment, aSyn monomers start to aggregate and form high molecular weight species. Afterwards, late endosomes fuse with lysosomes, where aSyn can be degraded. It is possible that, during any of those steps, aSyn is released to the cytoplasm and to the extracellular milieu, leading to its potential accumulation and spreading of pathology