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Updated: Jan 6, 2026
Isolation of Cortical Microglia with Preserved Immunophenotype and Functionality From Murine Neonates
Published on: January 30, 2014
MPP+ disorders Irg1-Itaconate axis to promote M1 polarization of microglia by activating succinate dehydrogenase
Lin-Yu Wang1, Yi-Yun Tang2,3, Wei Zou1,3,4
1The Affiliated Nanhua Hospital, Department of Neurology, Hengyang Medical School, University of South China, 336 S Dongfeng Road, Hengyang, 421002, Hunan, People's Republic of China.
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.
Insights
Parkinson's disease neuroinflammation involves microglial M1 polarization. MPP+ treatment disrupts the Irg1-Itaconate axis, activating SDH and promoting M1 polarization, offering a therapeutic target.
Area of Science:
- Neuroscience
- Immunology
- Cell Biology
Background:
- Microglial (MG) M1/M2 phenotypic switching is key in Parkinson's disease (PD) neuroinflammation.
- The precise mechanisms driving this switch remain incompletely understood.
Purpose of the Study:
- To investigate the mechanism by which MPP+ promotes microglial M1 polarization in PD.
- To explore the role of the Irg1-Itaconate axis and succinate dehydrogenase (SDH) in this process.
Main Methods:
- Utilized the BV2 microglial cell line treated with 1-methyl-4-phenylpyridinium ion (MPP+).
- Assessed the expression of immune response gene 1 (Irg1), itaconate levels, and SDH activation.
- Performed Irg1 knockdown experiments.
Main Results:
- MPP+ treatment upregulated Irg1, decreased itaconate, and enhanced SDH activation in BV2 cells, promoting M1 polarization.
- Itaconate inhibited SDH activation and reversed M1 polarization in MPP+-exposed cells.
- Irg1 knockdown exacerbated SDH activation and M1 polarization in MPP+-treated cells.
Conclusions:
- MPP+ disrupts the Irg1-Itaconate axis and activates SDH, driving microglial M1 polarization in PD.
- The Irg1-Itaconate axis presents a potential therapeutic target for mitigating neuroinflammation in Parkinson's disease.
