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.
Highlights
Parkinson’s disease (PD) is characterized by reduced dopamine levels in the striatum (STR) and the loss of dopaminergic neurons in the substantia nigra (SN)
Immunocytochemistry showed that the glial fibrillary acidic protein (GFAP) levels were significantly elevated by MPP+ and that a pretreatment with MHY2699 reduced these increases (p < 0.001, F2, 6 = 23.76) (Figure 1B,C)
Western blot analysis confirmed that MHY2699 reduced the MPP+ -induced GFAP expression (p < 0.05, F2, 6 = 9.104), indicating MHY2699 inhibited MPP+ -induced glial activation in primary astrocytes (Figure 1D)
Summary
Parkinson’s disease (PD) is characterized by reduced dopamine levels in the striatum (STR) and the loss of dopaminergic neurons in the substantia nigra (SN). Neuronal damage is a pathological hallmark of PD and other neurodegenerative diseases and is often caused by activation of the brain immune system. Considerable research has focused on finding therapeutic approaches to regulate neuroinflammation in neurodegenerative diseases [1]. Neuroinflammation plays important roles in the central nervous system (CNS) because it prompts the repair of damaged tissues, supplies nutrients, defends against external pathogens, and maintains homeostasis [2]. Microglia and astrocytes are unique cells in the CNS and are activated by external stimuli, such as pathogens and traumatic injury, to repair brain damage [3].
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