Alpha-synuclein functions as a negative regulator for expression of tyrosine hydroxylase.

Previous studies have shown that over-expression of alpha-Synuclein (alpha-Syn), a protein whose abnormality is implicated in the pathogenesis of Parkinson's disease (PD), reduces tyrosine hydroxylase (TH) expression and dopamine synthesis. To explore the possible mechanism for the regulation of TH expression by alpha-Syn, luciferase reporter gene carrying a -493/+27bp fragment of human TH gene (pGL3-TH520) and pcDNA carrying halpha-Syn gene (pcDNA-halpha-Syn) were co-transfected into T293 cells. The results showed that alpha-Syn was only detected in pcDNA-halpha-Syn-transfected cells but not in pcDNA vector control cells. In alpha-Syn-transfected cells, the luciferase activity was dramatically reduced compared with the vector control cells. These results suggest that alpha-Syn may function as a negative regulator for TH expression by affecting the activity of TH promoter.