α-Synuclein regulation of the dopaminergic transporter: a possible role in the pathogenesis of Parkinson's disease

AbstractParkinson's disease (PD) is a slow progressive neurodegenerative disorder. Recent evidence suggests a central role for α-synuclein, a protein of unknown function, in the genesis of PD. The phenomenon of selective degeneration of dopaminergic neurons in PD may be linked to the potential toxicity of dopamine itself and aberrations in the processes which regulate dopamine content may underlie the pathogenesis of this disease. Here, we review a vital role of α-synuclein in the modulation of dopamine transporter (DAT) function, and describe how disruption of this modulatory process permits increased re-uptake of high levels of intracellular dopamine by DAT, causing profound neurotoxicity