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Front. Neurosci. | doi: 10.3389/fnins.2019.00276

Epigenetic analysis in human neurons: considerations for disease modeling in PD

 Laura De Boni1, 2 and Ullrich Wüllner3, 4*
  • 1Brigham and Women's Hospital, Harvard Medical School, United States
  • 2Harvard Medical School, United States
  • 3German Center for Neurodegenerative Diseases (DZNE), Germany
  • 4Universitätsklinikum Bonn, Germany

Parkinson’s disease (PD) is the second most common neurodegenerative disorder after Alzheimer’s disease. Most PD cases are considered to be sporadic and despite considerable scientific effort, the underlying cause(s) still remains enigmatic. In particular, it is unknown to which extent epigenetic alterations contribute to the pathophysiology of this devastating disorder. This is partly due to the fact that appropriate PD models are not yet available. Moreover, epigenetic patterns and mechanisms are species specific and murine systems reflect only a few of the idiosyncrasies of human neurons. For several years now, patient-specific stem cell-derived neural and non-neural cells have been employed to overcome this limitation allowing the analysis and establishment of humanized disease models for PD. Thus, several studies tried to dissect epigenetic alterations such as aberrant DNA methylation or microRNA patterns using Lund Human Mesencephalic cell lines (LUHMES) or neurons derived from (patient-specific) induced pluripotent stem cells. These studies demonstrate, that human neurons have the potential to be used as model systems for the study of epigenetic modifications in PD such as characterizing epigenetic changes, correlating epigenetic changes to gene expression alterations and hopefully using these insights for the development of novel therapeutics. However, more research is required to define the epigenetic (age-asssociated) landscape of human in vitro neurons and compare these to native neurons before they can be established as suitable models for epigenetic studies in PD. In this review, we summarize the knowledge about epigenetic studies performed on human neuronal PD models, and we discuss advantages and current limitations of these (stem cell-derived) neuronal models for the study of epigenetic alterations in PD.

Keywords: Stem Cells, IPSC, Parkinson's disease, epigenetics, Neurons, human

Received: 05 Jul 2018; Accepted: 08 Mar 2019.

Edited by:

Aideen M. Sullivan, University College Cork, Ireland

Reviewed by:

Mario Ezquerra, August Pi i Sunyer Biomedical Research Institute (IDIBAPS), Spain
Maeve A. Caldwell, Trinity College Dublin, Ireland  

Copyright: © 2019 De Boni and Wüllner. 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: Prof. Ullrich Wüllner, German Center for Neurodegenerative Diseases (DZNE), Bonn, 53127, North Rhine-Westphalia, Germany, Ullrich.wuellner@ukbonn.de