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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 RyuHye-Yeon ParkJun GoYong-Hoon KimJung Hwan HwangDong Hee ChoiJung-Ran NohM RheeP L HanChul Ho LeeKyoung Shim Kim

Publisher 

Springer Verlag (Germany)

Issue Date 

2018

Citation 

Journal of Neural Transmission

Keywords 

6-HydroxydopamineAnacardic acidCurcuminGarcinolHAT inhibitorL-DOPA-induced dyskinesia

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.

ISSN 

0300-9564

Link 

http://dx.doi.org/10.1007/s00702-018-1902-4

Appears in Collections

1. Journal Articles > Journal Articles

Registered Date

2019-05-02


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