Epigenetic processes in Parkinson disease

Numerous investigations performed over the last 20 years revealed various epigenetic modifications in both postmortem brain samples and in peripheral tissues of individuals with Parkinson disease (PD), as well as in neuronal and animal models of the disease. These include changes in DNA methylation and hydroxymethylation, histone-tail modifications, and a dysregulated expression of both short- and long-noncoding RNA molecules. Overall, there is no doubt that epigenetic modifications occur within the neurodegenerative process linked to PD, resulting in altered expression of PD-linked genes. However, it is not yet completely clear which of these epigenetic changes are a consequence of the neurodegenerative process and which are instead early events capable of contributing to it. Indeed, studies in peripheral tissues of patients at different disease stages are attempting to provide early epigenetic biomarkers of clinical utility. Similarly, the epigenetic properties of ascertained PD risk factors, including metals, herbicides, and pesticides, are being tested in animal and cell culture models to detect environmentally induced epigenetic changes potentially contributing to the disease. The potential of epigenetic treatments and epigenome editing for PD is another area of active research.