Figure 1.

Implicated pathways for α-syn toxicity. To the left, healthy cellular pathways are illustrated, while to the right examples of how these pathways are perturbed in Parkinson’s disease (PD) are shown. Under normal circumstances, autophagic and lysosomal clearance degrades protein and other debris in the cell. In PD these pathways are blocked causing an accumulation of aggregated protein that could itself lead to more aggregation. In healthy cells, endoplasmic reticulum (ER) function is preserved, but in PD ER stress leads to calcium efflux into the cytoplasm. While in healthy cells mitochondrial function and oxidative balance are maintained, in PD the electron transport chain (ETC) and mitochondria function are compromised which causes an increase in reactive oxygen species (ROS) that leads to oxidative stress. Finally, in PD α-syn may interact with synaptobrevin-2, leading to synaptic dysfunction.