The epigenome as a therapeutic target for Parkinson's disease
| dc.contributor.author | Hegarty, Shane V. | |
| dc.contributor.author | Sullivan, Aideen M. | |
| dc.contributor.author | O'Keeffe, Gerard W. | |
| dc.contributor.funder | Irish Research Council | en |
| dc.contributor.funder | National University of Ireland | en |
| dc.contributor.funder | Science Foundation Ireland | en |
| dc.date.accessioned | 2017-01-04T12:31:30Z | |
| dc.date.available | 2017-01-04T12:31:30Z | |
| dc.date.issued | 2016-11 | |
| dc.date.updated | 2017-01-04T12:13:21Z | |
| dc.description.abstract | Parkinson’s disease (PD) is a common, progressive neurodegenerative disease characterised by degeneration of nigrostriatal dopaminergic neurons, aggregation of α-synuclein and motor symptoms. Current dopamine-replacement strategies provide symptomatic relief, however their effectiveness wear off over time and their prolonged use leads to disabling side-effects in PD patients. There is therefore a critical need to develop new drugs and drug targets to protect dopaminergic neurons and their axons from degeneration in PD. Over recent years, there has been robust evidence generated showing that epigenetic dysregulation occurs in PD patients, and that epigenetic modulation is a promising therapeutic approach for PD. This article first discusses the present evidence implicating global, and dopaminergic neuron-specific, alterations in the methylome in PD, and the therapeutic potential of pharmacologically targeting the methylome. It then focuses on another mechanism of epigenetic regulation, histone acetylation, and describes how the histone acetyltransferase (HAT) and histone deacetylase (HDAC) enzymes that mediate this process are attractive therapeutic targets for PD. It discusses the use of activators and/or inhibitors of HDACs and HATs in models of PD, and how these approaches for the selective modulation of histone acetylation elicit neuroprotective effects. Finally, it outlines the potential of employing small molecule epigenetic modulators as neuroprotective therapies for PD, and the future research that will be required to determine and realise this therapeutic potential. | en |
| dc.description.sponsorship | Irish Research Council (Grant Number R15897); National University of Ireland (Grant Number R16189); Science Foundation Ireland (Grant Number 15/CDA/13498) | en |
| dc.description.status | Peer reviewed | en |
| dc.description.version | Published Version | en |
| dc.format.mimetype | application/pdf | en |
| dc.identifier.citation | Hegarty, S. V., Sullivan, A. M. and O'Keeffe, G. W. (2016) 'The epigenome as a therapeutic target for Parkinson's disease', Neural Regeneration Research, 11(11), pp. 1735-1738. doi:10.4103/1673-5374.194803 | en |
| dc.identifier.doi | 10.4103/1673-5374.194803 | |
| dc.identifier.endpage | 1738 | en |
| dc.identifier.issn | 1673-5374 | |
| dc.identifier.issued | 11 | en |
| dc.identifier.journaltitle | Neural Regeneration Research | en |
| dc.identifier.startpage | 1735 | en |
| dc.identifier.uri | https://hdl.handle.net/10468/3420 | |
| dc.identifier.volume | 11 | en |
| dc.language.iso | en | en |
| dc.publisher | Medknow Publications | en |
| dc.rights | © 2016, Neural Regeneration Research. This is an open access article distributed under the terms of the Creative Commons Attribution-NonCommercialShareAlike 3.0 License, which allows others to remix, tweak, and build upon the work non-commercially, as long as the author is credited and the new creations are licensed under the identical terms. | en |
| dc.rights.uri | https://creativecommons.org/licenses/by-nc-sa/3.0/ | en |
| dc.subject | Epigenetics | en |
| dc.subject | Methylation | en |
| dc.subject | Acetylation | en |
| dc.subject | Histone acetyltransferase | en |
| dc.subject | Histone deacetylase | en |
| dc.subject | Small molecules | en |
| dc.subject | Parkinson's disease | en |
| dc.title | The epigenome as a therapeutic target for Parkinson's disease | en |
| dc.type | Article (peer-reviewed) | en |
