CpG Demethylation Enhances Alpha-Synuclein Expression and Affects the Pathogenesis of Parkinsons DiseaseReportar como inadecuado




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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.



Autor: Lumine Matsumoto, Hiroshi Takuma, Akira Tamaoka, Hiroshi Kurisaki, Hidetoshi Date, Shoji Tsuji, Atsushi Iwata

Fuente: http://plos.srce.hr/



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