Implications of DNA Methylation in Parkinson’s Disease

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.

50‐Hz MF does not affect global DNA methylation of SH‐SY5Y cells treated with the neurotoxin MPP+

“…Besides oxidative stress, the etiopathogenesis of neurodegenerative diseases recently encompassed the involvement of epigenetic machinery [Ammal Kaidery et al, ]. In PD, DNA methylation has attracted particular attention, and different studies have identified the occurrence of aberrant patterns of global DNA methylation in brains from PD patients [Chuang et al, ; Miranda‐Morales et al, ]. Here, we evaluated whether exposure to 50‐Hz (1 mT) MF might affect global DNA methylation of dopaminergic‐like cells.…”

“…In PD patients, alteration of global and promoter‐specific DNA methylation has been reported [Chuang et al, ; Miranda‐Morales et al, ]. In particular, in post mortem brains of PD patients, the α‐synuclein gene promoter was found to be highly hypo‐methylated [Wullner et al, ].…”

Prospects for incorporation of epigenetic biomarkers in human health and environmental risk assessment of chemicals

“…DNAm is a very stable mechanism, capable of providing reliable measurements from a wide range of biological materials, such as tissue, blood (plasma and serum), sputum, urine, etc., even after long‐term storage (Nogueira da Costa & Herceg, ; Lorincz, ). In the context of therapeutics and biomarker discovery, methylation assays are easy to perform and automate and, in several cases, concordant methylation alterations have been found in different tissues of the human body (Nogueira da Costa & Herceg, ; Masliah et al ., ; Lorincz, ; Miranda‐Morales et al ., ). From an operational point of view, technologies to measure DNAm marks and patterns are now “reproducible, cost‐efficient and amenable to high‐throughput processing” (Ladd‐Acosta, , p. 118).…”

Intranasal perillyl alcohol therapy improves survival of patients with recurrent glioblastoma harboring mutant variant for MTHFR rs1801133 polymorphism

“…Currently available treatments for rGBM are unable to effectively overcome the high intratumoral cellular and molecular heterogeneity to elicit sustained tumor regression. Disease complexity may be further enhanced by detrimental effects of cytotoxic chemotherapy and ionizing radiation on genetic and epigenetic stability [15,22,26].Since tumor-associated changes in the gDNA methylation status is replicated in gDNA obtained from peripheral blood cells of cancer patients [38][39][40], analysis of gDNA global methylation status using peripheral mononuclear cells from rGBM patients could be potentially used as a non-invasive prognostic biomarker, representing a valuable circulating screening tool that better represents the dynamic nature of such intracranial malignancy [41].…”