Abstract
It has been 200 years since Parkinson’s disease (PD) was first described, yet many aspects of its etiopathogenesis remain unclear. PD is a progressive and complex neurodegenerative disorder caused by genetic and environmental factors including aging, nutrition, pesticides and exposure to heavy metals. DNA methylation may be altered in response to some of these factors; therefore, it is proposed that epigenetic mechanisms, particularly DNA methylation, can have a fundamental role in gene–environment interactions that are related with PD. Epigenetic changes in PD-associated genes are now widely studied in different populations, to discover the mechanisms that contribute to disease development and identify novel biomarkers for early diagnosis and future pharmacological treatment. While initial studies sought to find associations between promoter DNA methylation and the regulation of associated genes in PD brain tissue, more recent studies have described concordant DNA methylation patterns between blood and brain tissue DNA. These data justify the use of peripheral blood samples instead of brain tissue for epigenetic studies. Here, we summarize the current data about DNA methylation changes in PD and discuss the potential of DNA methylation as a potential biomarker for PD. Additionally, we discuss environmental and nutritional factors that have been implicated in DNA methylation. Although the search for significant DNA methylation changes and gene expression analyses of PD-associated genes have yielded inconsistent and contradictory results, epigenetic modifications remain under investigation for their potential to reveal the link between environmental risk factors and the development of PD.
Highlights
Parkinson’s disease (PD) is the second most common chronic neurodegenerative disease in the elderly population
Analysis of DNA methylation profiles of blood clearly distinguishes PD patients from healthy subjects or subjects with other disorders. These results suggest that, firstly, peripheral blood may be a valid surrogate for brain tissue samples, and secondly, epigenetic changes could potentially serve as biomarkers for the diagnosis of PD
DNA methylation frequency of the NPAS2 promoter was significantly decreased in PD patients, suggesting that its promoter DNA methylation may contribute to the expression of clock genes in PD (Lin et al, 2012)
Summary
Parkinson’s disease (PD) is the second most common chronic neurodegenerative disease in the elderly population. Epigenetic factors are chemical modifications of chromatin or its regulatory proteins that do not change the underlying genomic sequence These modifications can modulate gene expression, allowing differentiation into different cellular phenotypes by driving tissue-specific expression patterns. Access to brain samples for research is limited, so the focus has been on finding a more accessible tissue, such as peripheral blood, as a surrogate for brain tissue For this purpose, a genome-wide study examined DNA methylation changes in PD patients by collecting fresh post-mortem brain and blood samples from PD patients and age-matched healthy subjects (Masliah et al, 2013). Analysis of DNA methylation profiles of blood clearly distinguishes PD patients from healthy subjects or subjects with other disorders These results suggest that, firstly, peripheral blood may be a valid surrogate for brain tissue samples, and secondly, epigenetic changes could potentially serve as biomarkers for the diagnosis of PD. We discuss the current evidence for DNA methylation changes in PD, including the involvement of nutrition and environmental factors
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