Fig. 2

Alpha-synuclein oligomers and cytosolic DA amplify each other and synergistically contribute to oxidative stress. 1) DA anabolism enzyme, MAO, turns DA into DOPAL, that later can be converted into less reactive DOPAC by another enzyme. 2) DOPAL induces α-synuclein oligomerization and prevents fibril formation. 3) DOPAL modified α-synuclein oligomers create pore-like structure in the synaptic vesicle membrane, causing DA leakage into cytosol. 4) α-synuclein oligomers are also known to negatively regulate synaptic vesicle release by preventing SNARE formation and vesicle docking. This provides more DA vesicles that can be targeted by DOPAL-α-synuclein oligomers. 5) Oxidation of cytosolic DA produces DAQ. 6) DAQ reacts with cysteine residues of mitochondrial proteins that results in mitochondria depolarization and further ROS production