A small molecule activator of p300/CBP histone acetyltransferase promotes survival and neurite growth in a cellular model of Parkinson’s disease
| 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.contributor.funder | Irish Research Council for Science, Engineering and Technology | en |
| dc.contributor.funder | National University of Ireland | en |
| dc.date.accessioned | 2016-10-14T09:02:08Z | |
| dc.date.available | 2016-10-14T09:02:08Z | |
| dc.date.issued | 2016-06-02 | |
| 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.description.status | Peer reviewed | en |
| dc.description.version | Accepted Version | en |
| dc.format.mimetype | application/pdf | en |
| 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.doi | 10.1007/s12640-016-9636-2 | |
| dc.identifier.endpage | 520 | en |
| dc.identifier.issn | 1029-8428 | |
| dc.identifier.issued | 3 | en |
| dc.identifier.journaltitle | Neurotoxicity Research | en |
| dc.identifier.startpage | 510 | en |
| dc.identifier.uri | https://hdl.handle.net/10468/3180 | |
| dc.identifier.volume | 30 | 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 |
