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DNA methylation levels of α-synuclein intron 1 in the aging brain
- Source :
- Neurobiology of aging 36(12), 3334.e7-3334.e11 (2015). doi:10.1016/j.neurobiolaging.2015.08.028
- Publication Year :
- 2015
- Publisher :
- Elsevier BV, 2015.
-
Abstract
- DNA methylation patterns change with age, and aging itself is a major confounding risk factor for Parkinson's disease (PD). Duplication and triplication, that is, increased expression of the α-synuclein (SNCA) gene, cause familial PD, and demethylation of SNCA intron 1 has been shown to result in increased expression of SNCA. We thus hypothesized that age-related alterations of SNCA methylation might underly the increased susceptibility toward PD in later life. The present study sought to determine (1) whether alterations of SNCA intron 1 methylation occurred during aging, (2) whether the methylation pattern differed between men and women, and (3) whether purified neurons compared with non-neuronal cells exhibited different methylation patterns. The analysis of DNA from brain tissue and fluorescence activated cell sorting-sorted purified neurons of 41 individuals revealed only a minor increase of SNCA intron 1 DNA methylation levels in presumably healthy individuals during aging but no significant difference between men and women. Interestingly enough, methylation of SNCA intron 1 was higher in neurons compared with non-neuronal cells, although non-neuronal cells express lower levels of SNCA. Therefore, the normal pattern of SNCA methylation during aging should not result in increased expression of α-synuclein protein. It is thus likely that additional, yet not identified, mechanisms contribute to the tissue specificity of SNCA expression and the presumed dysregulation in PD.
- Subjects :
- Adult
Male
Aging
Adolescent
genetics [Introns]
Biology
genetics [DNA Methylation]
Young Adult
chemistry.chemical_compound
genetics [Parkinson Disease]
Risk Factors
Gene duplication
Humans
Aging brain
ddc:610
metabolism [alpha-Synuclein]
SNCA protein, human
Child
Gene
Genetic Association Studies
Aged
Aged, 80 and over
Alpha-synuclein
General Neuroscience
Infant, Newborn
Intron
Brain
Infant
Parkinson Disease
Methylation
DNA Methylation
Middle Aged
Molecular biology
Introns
chemistry
metabolism [Brain]
genetics [Aging]
Child, Preschool
DNA methylation
genetics [alpha-Synuclein]
alpha-Synuclein
Female
Neurology (clinical)
Geriatrics and Gerontology
DNA
Developmental Biology
Subjects
Details
- ISSN :
- 01974580
- Volume :
- 36
- Database :
- OpenAIRE
- Journal :
- Neurobiology of Aging
- Accession number :
- edsair.doi.dedup.....47c68f9708f6f3bf30e8cd6ee6f693a7