[Neurodegeneration and epigenetics].
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. 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. This CpG region may function as an intronic regulatory element for the SNCA gene. Our findings suggest that a novel epigenetic regulatory mechanism controlling SNCA expression influences PD pathogenesis.
Department of Molecular Neuroscience on Neurodegeneration, Graduate School of Medicine, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-0033, Japan. iwata-tky@umin.ac.jp
Atsushi
A
Iwata
D000818:Animals; D018899:CpG Islands / Q000235:genetics; D044127:Epigenesis, Genetic / Q000235:genetics* / Q000502:physiology; D015870:Gene Expression / Q000235:genetics* / Q000502:physiology; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D006801:Humans; D019636:Neurodegenerative Diseases / Q000235:genetics*; D051844:alpha-Synuclein / Q000235:genetics
D051844:alpha-Synuclein