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01-09-2018 | Neurology and Preclinical Neurological Studies - Original Article

Effects of histone acetyltransferase inhibitors on l-DOPA-induced dyskinesia in a murine model of Parkinson’s disease

Authors: Young-Kyoung Ryu, Hye-Yeon Park, Jun Go, Yong-Hoon Kim, Jung Hwan Hwang, Dong-Hee Choi, Jung-Ran Noh, Myungchull Rhee, Pyung-Lim Han, Chul-Ho Lee, Kyoung-Shim Kim

Published in: Journal of Neural Transmission | Issue 9/2018

Abstract

Histone acetylation is a key regulatory factor for gene expression in cells. Modulation of histone acetylation by targeting of histone acetyltransferases (HATs) effectively alters many gene expression profiles and synaptic plasticity in the brain. However, the role of HATs on l-DOPA-induced dyskinesia of Parkinson’s disease (PD) has not been reported. Our aim was to determine whether HAT inhibitors such as anacardic acid, garcinol, and curcumin from natural plants reduce severity of l-DOPA-induced dyskinesia using a unilaterally 6-hydroxydopamine (6-OHDA)-lesioned PD mouse model. Anacardic acid 2 mg/kg, garcinol 5 mg/kg, or curcumin 100 mg/kg co-treatment with l-DOPA significantly reduced the axial, limb, and orofacial (ALO) score indicating less dyskinesia with administration of HAT inhibitors in 6-OHDA-lesioned mice. Additionally, l-DOPA’s efficacy was not altered by the compounds in the early stage of treatment. The expression levels of c-Fos, Fra-2, and Arc were effectively decreased by administration of HAT inhibitors in the ipsilateral striatum. Our findings indicate that HAT inhibitor co-treatment with l-DOPA may have therapeutic potential for management of l-DOPA-induced dyskinesia in patients with PD.

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Title: Effects of histone acetyltransferase inhibitors on l-DOPA-induced dyskinesia in a murine model of Parkinson’s disease
Authors: Young-Kyoung Ryu
Hye-Yeon Park
Jun Go
Yong-Hoon Kim
Jung Hwan Hwang
Dong-Hee Choi
Jung-Ran Noh
Myungchull Rhee
Pyung-Lim Han
Chul-Ho Lee
Kyoung-Shim Kim
Publication date: 01-09-2018
Publisher: Springer Vienna
Published in: Journal of Neural Transmission / Issue 9/2018
Print ISSN: 0300-9564
Electronic ISSN: 1435-1463
DOI: https://doi.org/10.1007/s00702-018-1902-4

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Effects of histone acetyltransferase inhibitors on l-DOPA-induced dyskinesia in a murine model of Parkinson’s disease

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