CpG demethylation enhances alpha-synuclein expression and affects the pathogenesis of Parkinson's disease.
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.


RESULTS
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
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.
Division of Neuroscience, Department of Neurology, Graduate School of Medicine, The University of Tokyo, Bunkyo, Tokyo, Japan.
Lumine
L
Matsumoto
Hiroshi
H
Takuma
Akira
A
Tamaoka
Hiroshi
H
Kurisaki
Hidetoshi
H
Date
Shoji
S
Tsuji
Atsushi
A
Iwata
D000368:Aged; D000369:Aged, 80 and over; D000818:Animals; D018899:CpG Islands / Q000235:genetics*; D019175:DNA Methylation; D004298:Dopamine / Q000494:pharmacology; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects; D020022:Genetic Predisposition to Disease; D057809:HEK293 Cells; D006367:HeLa Cells; D006801:Humans; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008875:Middle Aged; D010300:Parkinson Disease / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D011180:Postmortem Changes; D051844:alpha-Synuclein / Q000235:genetics* / Q000378:metabolism
D051844:alpha-Synuclein; D004298:Dopamine