Methylation regulates alpha-synuclein expression and is decreased in Parkinson's disease patients' brains.
Alpha-synuclein (SNCA) is a major risk gene for Parkinson's disease (PD), and increased SNCA gene dosage results in a parkinsonian syndrome in affected families. We found that methylation of human SNCA intron 1 decreased gene expression, while inhibition of DNA methylation activated SNCA expression. Methylation of SNCA intron 1 was reduced in DNA from sporadic PD patients' substantia nigra, putamen, and cortex, pointing toward a yet unappreciated epigenetic regulation of SNCA expression in PD.
Jowaed
Ahmad
A
Department of Neurology, Rheinische Friedrich-Wilhelms-Universität, Universitätsklinikum Bonn, D-53105 Bonn, Germany.
Schmitt
Ina
I
Kaut
Oliver
O
Wüllner
Ullrich
U
D000368:Aged; D002540:Cerebral Cortex / Q000378:metabolism*; D019175:DNA Methylation; D044127:Epigenesis, Genetic; D005260:Female; D020022:Genetic Predisposition to Disease; D006801:Humans; D007438:Introns; D008297:Male; D010300:Parkinson Disease / Q000235:genetics* / Q000378:metabolism; D011699:Putamen / Q000378:metabolism*; D013378:Substantia Nigra / Q000378:metabolism*; D051844:alpha-Synuclein / Q000235:genetics* / Q000378:metabolism
C497604:SNCA protein, human; D051844:alpha-Synuclein
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