Several single nucleotide polymorphisms (SNPs) and the Rep-1 microsatellite marker of the α-synuclein ( ) gene have consistently SNCA been shown to be associated with Parkinson's disease, but the functional relevance is unclear. Based on these findings we hypothesized that conserved cis-regulatory elements in the genomic region regulate SNCA expression of , and that SNPs in these regions could be functionally SNCA modulating the expression of , thus contributing to neuronal demise SNCA and

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... sposing to Parkinson's disease. In a pair-wise comparison of a 206kb genomic region encompassing the gene, we revealed 34 evolutionary conserved DNA sequences SNCA between human and mouse. All elements were cloned into reporter vectors and assessed for expression modulation in dual luciferase reporter assays. We found that 12 out of 34 elements exhibited either an enhancement or reduction of the expression of the reporter gene. Three elements upstream of the gene displayed an approximately 1.5 fold (p<0.009) increase SNCA in expression. Of the intronic regions, three showed a 1.5 fold increase and two others indicated a 2 and 2.5 fold increase in expression (p<0.002). Three elements downstream of the gene showed 1.5 fold and 2.5 SNCA fold increase (p<0.0009). One element downstream of had a SNCA reduced expression of the reporter gene of 0.35 fold (p<0.0009) of normal activity. Our results demonstrate that the gene contains cis-regulatory SNCA regions that might regulate the transcription and expression of . SNCA Further studies in disease-relevant tissue types will be important to understand the functional impact of regulatory regions and specific Parkinson's disease-associated SNPs and its function in the disease process.