A small molecule activator of p300/CBP histone acetyltransferase promotes survival and neurite growth in a cellular model of Parkinson’s disease

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dc.contributor.author Hegarty, Shane V.
dc.contributor.author O'Leary, Eimear
dc.contributor.author Solger, Franziska
dc.contributor.author Stanicka, Joanna
dc.contributor.author Sullivan, Aideen M.
dc.contributor.author O'Keeffe, Gerard W.
dc.date.accessioned 2016-10-14T09:02:08Z
dc.date.available 2016-10-14T09:02:08Z
dc.date.issued 2016-06-02
dc.identifier.citation Hegarty, S.V., O’Leary, E., Solger, F., Stanicka, J., Sullivan, A.M. and O’Keeffe, G.W. (2016) 'A small molecule activator of p300/CBP histone acetyltransferase promotes survival and neurite growth in a cellular model of Parkinson’s disease', Neurotoxicity Research, 30(3) pp.510-520. doi:10.1007/s12640-016-9636-2 en
dc.identifier.volume 30 en
dc.identifier.issued 3 en
dc.identifier.startpage 510 en
dc.identifier.endpage 520 en
dc.identifier.issn 1029-8428
dc.identifier.uri http://hdl.handle.net/10468/3180
dc.identifier.doi 10.1007/s12640-016-9636-2
dc.description.abstract Parkinson’s disease (PD) is a progressive neurodegenerative disease characterised by motor and non-motor symptoms, resulting from the degeneration of nigrostriatal dopaminergic neurons and peripheral autonomic neurons. Given the limited success of neurotrophic factors in clinical trials, there is a need to identify new small molecule drugs and drug targets to develop novel therapeutic strategies to protect all neurons that degenerate in PD. Epigenetic dysregulation has been implicated in neurodegenerative disorders, while targeting histone acetylation is a promising therapeutic avenue for PD. We and others have demonstrated that histone deacetylase inhibitors have neurotrophic effects in experimental models of PD. Activators of histone acetyltransferases (HAT) provide an alternative approach for the selective activation of gene expression, however little is known about the potential of HAT activators as drug therapies for PD. To explore this potential, the present study investigated the neurotrophic effects of CTPB (N-(4-chloro-3-trifluoromethyl-phenyl)-2-ethoxy-6-pentadecyl-benzamide), which is a potent small molecule activator of the histone acetyltransferase p300/CBP, in the SH-SY5Y neuronal cell line. We report that CTPB promoted the survival and neurite growth of the SH-SY5Y cells, and also protected these cells from cell death induced by the neurotoxin 6-hydroxydopamine. This study is the first to investigate the phenotypic effects of the HAT activator CTPB, and to demonstrate that p300/CBP HAT activation has neurotrophic effects in a cellular model of PD. en
dc.description.sponsorship Irish Research Council (Grant R15897); National University of Ireland (Grant R16189) en
dc.format.mimetype application/pdf en
dc.language.iso en en
dc.publisher Springer International Publishing en
dc.rights © 2016, Springer Science+Business Media, New York. The final publication is available at Springer via http://dx.doi.org/10.1007/s12640-016-9636-2 en
dc.subject Parkinson’s disease en
dc.subject Neurotrophic therapy en
dc.subject Epigenetic regulation en
dc.subject p300/CBP histone acetyltransferase en
dc.subject CTPB en
dc.subject Neuronal survival and growth en
dc.title A small molecule activator of p300/CBP histone acetyltransferase promotes survival and neurite growth in a cellular model of Parkinson’s disease en
dc.type Article (peer-reviewed) en
dc.internal.authorcontactother Shane Hegarty, Anatomy and Neuroscience, University College Cork, Cork, Ireland. +353-21-490-3000 Email: shane.hegarty@ucc.ie en
dc.internal.availability Full text available en
dc.check.info Access to this article is restricted until 12 months after publication by request of the publisher. en
dc.check.date 2017-06-02
dc.description.version Accepted Version en
dc.internal.rssid 350954507
dc.contributor.funder Irish Research Council for Science, Engineering and Technology en
dc.contributor.funder National University of Ireland en
dc.description.status Peer reviewed en
dc.identifier.journaltitle Neurotoxicity Research en
dc.internal.IRISemailaddress shane.hegarty@ucc.ie
dc.internal.IRISemailaddress shane.hegarty@ucc.ie en

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