Methylation Regulates Alpha-Synuclein Expression and Is Decreased in Parkinson's Disease Patients' Brains

• DOI: 10.1523/jneurosci.6119-09.2010
• Publication Date: 2010-05-05T19:47:39Z
• Authors: Ahmad Jowaed; Ina Schmitt; Oliver Kaut; Ullrich Wüllner
• Keywords: Cerebral Cortex; Male; 0301 basic medicine; Putamen; Parkinson Disease; DNA Methylation; Introns; Epigenesis, Genetic; Substantia Nigra; 03 medical and health sciences; alpha-Synuclein; Humans; Female; Genetic Predisposition to Disease; Aged

Alpha-synuclein (SNCA) is a major risk gene for Parkinson's disease (PD), and increasedSNCAgene dosage results in a parkinsonian syndrome in affected families. We found that methylation of humanSNCAintron 1 decreased gene expression, while inhibition of DNA methylation activated SNCA expression. Methylation ofSNCAintron 1 was reduced in DNA from sporadic PD patients' substantia nigra, putamen, and cortex, pointing toward a yet unappreciated epigenetic regulation ofSNCAexpression in PD.