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

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-κB. 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.

Anti-Inflammatory Effect of IKK-Activated GSK-3β Inhibitory Peptide Prevented Nigrostriatal Neurodegeneration in the Rodent Model of Parkinson’s Disease

“…Previous studies have demonstrated that MPP + neurotoxin triggers glial activation and neuroinflammation by increasing levels of GFAP (glial fibrillary acidic protein) and proinflammatory cytokines in primary astrocytes [17][18][19]. We pre-treated primary astrocytes with 1 µM of IAGIP for 6 h and then co-treated them with 200 µM of MPP + for 24 h. Immunocytochemistry (ICC) and Western blotting showed that IAGIP suppressed MPP +induced GFAP increases in primary astrocytes (Figure 1A-C).…”