The epigenome as a therapeutic target for Parkinson's disease

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dc.contributor.author Hegarty, Shane V.
dc.contributor.author Sullivan, Aideen M.
dc.contributor.author O'Keeffe, Gerard W.
dc.date.accessioned 2017-01-04T12:31:30Z
dc.date.available 2017-01-04T12:31:30Z
dc.date.issued 2016-11
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.volume 11 en
dc.identifier.issued 11 en
dc.identifier.startpage 1735 en
dc.identifier.endpage 1738 en
dc.identifier.issn 1673-5374
dc.identifier.uri http://hdl.handle.net/10468/3420
dc.identifier.doi 10.4103/1673-5374.194803
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.format.mimetype application/pdf 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
dc.internal.authorcontactother Shane Hegarty, Department Of Anatomy & Neuroscience, University College Cork, Cork, Ireland. +353-21-490-3000 Email: shane.hegarty@ucc.ie en
dc.internal.availability Full text available en
dc.date.updated 2017-01-04T12:13:21Z
dc.description.version Published Version en
dc.internal.rssid 372727933
dc.contributor.funder Irish Research Council en
dc.contributor.funder National University of Ireland en
dc.contributor.funder Science Foundation Ireland en
dc.description.status Peer reviewed en
dc.identifier.journaltitle Neural Regeneration Research en
dc.internal.copyrightchecked Yes en
dc.internal.licenseacceptance Yes en
dc.internal.IRISemailaddress shane.hegarty@ucc.ie en


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© 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. Except where otherwise noted, this item's license is described as © 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.
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