Entanglement of Genetics and Epigenetics in Parkinson's Disease

Parkinson disease (PD) is a common neurodegenerative disorder that progresses with age, with an increasing number of symptoms. Some of the efforts to understand PD progression have been focusing on the regulation of epigenetic mechanisms, that generally include small molecular modifications to the DNA and histones that are essential for regulating gene activity. Here, we have pointed out difficulties to untangle genetic and epigenetic mechanisms, and reviewed several studies that have aimed for untangling. Some of those have enabled more solid claims on independent roles for epigenetic mechanisms. Hereby, evidence that specific DNA hydroxymethylation, global hyperacetylation, and histone deacetylase (HDAC) dependent regulation of SNCA, one of the hallmark genes involved in PD, have become more prominent from the current perspective, than mechanisms that directly involve DNA methylation. In the absence of current epigenetic clinical targets to counteract PD progression, we also hypothesize how several mechanisms may affect local and global epigenetics in PD neurons, including inflammation, oxidative stress, autophagy and DNA repair mechanisms which may lead to future therapeutic targets.