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CpG Demethylation Enhances Alpha-Synuclein Expression and Affects the Pathogenesis of Parkinson's Disease

Lumine MatsumotoDivision of Neuroscience, Department of Neurology, Graduate School of Medicine, The University of Tokyo, Bunkyo, Tokyo, JapanHiroshi TakumaDepartment of Neurology, University of Tsukuba, Tsukuba, Ibaraki, JapanAkira TamaokaDepartment of Neurology, University of Tsukuba, Tsukuba, Ibaraki, JapanHiroshi KurisakiDepartment of Neurology, National Hospital Organization Tokyo Hospital, Kiyose, Tokyo, JapanHidetoshi DateDivision of Neuroscience, Department of Neurology, Graduate School of Medicine, The University of Tokyo, Bunkyo, Tokyo, JapanShoji TsujiDivision of Neuroscience, Department of Neurology, Graduate School of Medicine, The University of Tokyo, Bunkyo, Tokyo, JapanAtsushi IwataDepartment of Molecular Neuroscience on Neurodegeneration, Graduate School of Medicine, The University of Tokyo, Bunkyo, Tokyo, Japan

2010en

ABI

Annotatsiya

BACKGROUND: Alpha-synuclein (SNCA) gene expression is an important factor in the pathogenesis of Parkinson's disease (PD). Gene multiplication can cause inherited PD, and promoter polymorphisms that increase SNCA expression are associated with sporadic PD. CpG methylation in the promoter region may also influence SNCA expression. METHODOLOGY/PRINCIPAL FINDINGS: By using cultured cells, we identified a region of the SNCA CpG island in which the methylation status altered along with increased SNCA expression. Postmortem brain analysis revealed regional non-specific methylation differences in this CpG region in the anterior cingulate and putamen among controls and PD; however, in the substantia nigra of PD, methylation was significantly decreased. CONCLUSIONS/SIGNIFICANCE: This CpG region may function as an intronic regulatory element for SNCA gene. Our findings suggest that a novel epigenetic regulatory mechanism controlling SNCA expression influences PD pathogenesis.

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DOI: 10.1371/journal.pone.0015522

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