Entanglement of Genetics and Epigenetics in Parkinson’s Disease
- 1University of Amsterdam, Netherlands
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.
Keywords: Parkinson, Brain, development, neurdegeneration, Genetics, epigenetics
Received: 27 Jul 2018;
Accepted: 08 Mar 2019.
Edited by:Shane V. Hegarty, Boston Children's Hospital, Harvard Medical School, United States
Reviewed by:Petr A. Slominsky, Institute of Molecular Genetics (RAS), Russia
Ahmed Negida, Faculty of Medicine, Zagazig University, Egypt
Copyright: © 2019 van Heesbeen and Smidt. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: Dr. Marten P. Smidt, University of Amsterdam, Amsterdam, 1012 WX, Netherlands, email@example.com