Neuroprotective and anti-inflammatory effects of E11 in an in vitro Parkinson’s disease model

초록

Drug repurposing not only has several advantages over traditional drug development strategies but also offers new therapeutic alternatives for incurable diseases, including Parkinson’s disease, which is characterized by dopaminergic neuronal death. E11 is an antiplatelet agent used to treat acute coronary syndrome as an irreversible P2Y12 ADP receptor antagonist by ADP binding. E11 possesses antioxidant properties in atherosclerotic disease and inhibits pro-inflammatory T-cell response in humans. However, little is known about its potential antioxidant and anti-inflammatory effects in neuronal cells. This study aimed to investigate whether E11 has neuroprotective and anti-inflammatory effects in primary cortical neurons and BV-2 microglial cells. Proteomic analyses showed that various signaling pathways related to apoptotic cell death and neuroinflammation were altered by E11 treatment in 1-methyl-4- phenylpyridinium-treated primary cortical neurons and lipopolysaccharide-treated BV-2 microglial cells. In vitro studies demonstrated that E11 exerts neuroprotective and anti-inflammatory effects by inhibiting the mitogen-activated protein kinase signaling pathway. In addition, E11 ameliorated ROS production and mitochondrial dysfunction in primary cortical neurons. Therefore, this study proposes that E11 has neuroprotective and anti-inflammatory effects in an in vitro Parkinson’s disease model.