Figure 2.
Effects of α-synuclein on dopamine homeostasis in the presynaptic terminal. Dopamine is synthesized in the cytoplasm by the action of tyrosine hydroxylase (TH) and amino acid decarboxylase (AADC). (i) α-Synuclein has been shown to regulate the activity of these enzymes [35,36,43]. (ii) Once synthesized, dopamine is immediately sequestered into vesicles by the vesicular monoamine transporter 2 (VMAT2). Several lines of evidence suggest that α-synuclein is involved in regulating synaptic vesicle function and dopamine release into the synaptic cleft [51–53]. (iii) Dopaminergic signaling at the synapse is terminated by the reuptake of dopamine via the dopamine transporter (DAT), with co-transport of two Na+ and one Cl− ions. Studies in cell culture systems have shown that α-synuclein is necessary for the trafficking of DAT to the cell surface [61–64].