Molecular biology reports · 2025
MPP+ disorders Irg1-Itaconate axis to promote M1 polarization of microglia by activating succinate dehydrogenase.
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Wang Lin-Yu, Tang Yi-Yun, Zou Wei, Zhang Ping, Tang Xiao-Qing, Zhang Ping
Аннотация
BACKGROUND: The microglial (MG) M1/M2 phenotypic switch plays a crucial role in the neuroinflammation of Parkinson's disease (PD), but the underlying mechanism remains unclear.
METHODS AND RESULTS: In this study, the BV2 microglial cell line was treated with 1 methyl 4 phenyl pyridinium ion (MPP+) to investigate the mechanism of how to promote microglial M1 polarization in PD. Our study demonstrated that the polarization of microglia was facilitated towards the M1 phenotype, with the expression of immune response gene 1 (Irg1) being upregulated, the level of itaconate decreased, and the activation of succinate dehydrogenase (SDH) was enhanced in MPP+-treated BV2 cells. Conversely, Itaconate inhibited the activation of SDH and reversed the M1 polarization in MPP+-exposed BV2 cells. Importantly, the knockdown of Irg1 augmented the activation of SDH and the M1 polarization in MPP+-exposed BV2 cells.
CONCLUSIONS: These results reveal that MPP+ disorders the Irg1-Itaconate axis and activates SDH, thereby promoting the M1 polarization of BV2 cells. These insights contribute toward a better understanding of the mechanism underlying the microglial M1 polarization in PD and identify the Irg1-Itaconate axis as a potential therapeutic strategy for treating neuroinflammation in PD.
METHODS AND RESULTS: In this study, the BV2 microglial cell line was treated with 1 methyl 4 phenyl pyridinium ion (MPP+) to investigate the mechanism of how to promote microglial M1 polarization in PD. Our study demonstrated that the polarization of microglia was facilitated towards the M1 phenotype, with the expression of immune response gene 1 (Irg1) being upregulated, the level of itaconate decreased, and the activation of succinate dehydrogenase (SDH) was enhanced in MPP+-treated BV2 cells. Conversely, Itaconate inhibited the activation of SDH and reversed the M1 polarization in MPP+-exposed BV2 cells. Importantly, the knockdown of Irg1 augmented the activation of SDH and the M1 polarization in MPP+-exposed BV2 cells.
CONCLUSIONS: These results reveal that MPP+ disorders the Irg1-Itaconate axis and activates SDH, thereby promoting the M1 polarization of BV2 cells. These insights contribute toward a better understanding of the mechanism underlying the microglial M1 polarization in PD and identify the Irg1-Itaconate axis as a potential therapeutic strategy for treating neuroinflammation in PD.