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Anti-Inflammatory Effects of the Novel Barbiturate Derivative MHY2699 in an MPTP-Induced Mouse Model of Parkinson's Disease

Authors
Lee, SeulahSuh, Yeon JiLee, YujeongYang, SeongukHong, Dong GeunThirumalai, DinakaranChang, Seung-CheolChung, Ki WungJung, Young-SukMoon, Hyung RyongChung, Hae YoungLee, Jaewon
Issue Date
Nov-2021
Publisher
MDPI
Keywords
Parkinson' s disease; neuroinflammation; MHY2699; barbiturate; MPTP
Citation
ANTIOXIDANTS, v.10, no.11
Journal Title
ANTIOXIDANTS
Volume
10
Number
11
URI
http://scholarworks.bwise.kr/kbri/handle/2023.sw.kbri/618
DOI
10.3390/antiox10111855
ISSN
2076-3921
Abstract
Parkinson's disease (PD) is one of the most common neurodegenerative disorders, and is caused by the death of dopamine neurons and neuroinflammation in the striatum and substantia nigra. Furthermore, the inflammatory response in PD is closely related to glial cell activation. This study examined the neuroprotective effects of the barbiturate derivative, MHY2699 [5-(4-hydroxy 3,5-dimethoxybenzyl)-2 thioxodihydropyrimidine-4,6(1H,5H)-dione] in a mouse model of PD. MHY2699 ameliorated MPP?-induced astrocyte activation and ROS production in primary astrocytes and inhibited the MPP?-induced phosphorylation of MAPK and NF-kappa B. The anti-inflammatory effects of MHY2699 in protecting neurons were examined in an MPTP-induced mouse model of PD. MHY2699 inhibited MPTP-induced motor dysfunction and prevented dopaminergic neuronal death, suggesting that it attenuated neuroinflammation. Overall, MHY2699 has potential as a neuroprotective treatment for PD.
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