2. Academic Validation
  3. MPP+ disorders Irg1-Itaconate axis to promote M1 polarization of microglia by activating succinate dehydrogenase

MPP+ disorders Irg1-Itaconate axis to promote M1 polarization of microglia by activating succinate dehydrogenase

  • Mol Biol Rep. 2025 Nov 24;53(1):115. doi: 10.1007/s11033-025-11191-x.
Lin-Yu Wang # 1,  Yi-Yun Tang # 2 3,  Wei Zou 1 3 4,  Ping Zhang 5 6 7,  Xiao-Qing Tang 8 9 10,  Ping Zhang 11
Affiliations

Affiliations

  • 1 The 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.
  • 2 Institute of Neuroscience & Department of Physiology, Hengyang Medical School, University of South China, 28 W Changsheng Road, Hengyang, 421001, Hunan, People's Republic of China.
  • 3 NHC Key Laboratory of Neurodegenerative Disease, University of South China), Hengyang, 421001, Hunan, People's Republic of China.
  • 4 Hengyang Key Laboratory of Parkinson's Disease Basic and Clinical Research, Hengyang, 202150084071, 421001, Hunan, People's Republic of China.
  • 5 The 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. [email protected].
  • 6 NHC Key Laboratory of Neurodegenerative Disease, University of South China), Hengyang, 421001, Hunan, People's Republic of China. [email protected].
  • 7 Hengyang Key Laboratory of Parkinson's Disease Basic and Clinical Research, Hengyang, 202150084071, 421001, Hunan, People's Republic of China. [email protected].
  • 8 Institute of Neuroscience & Department of Physiology, Hengyang Medical School, University of South China, 28 W Changsheng Road, Hengyang, 421001, Hunan, People's Republic of China. [email protected].
  • 9 NHC Key Laboratory of Neurodegenerative Disease, University of South China), Hengyang, 421001, Hunan, People's Republic of China. [email protected].
  • 10 The Second Affiliated Hospital, Brain Disease Research Institute of Neurological Medicine Center, Hengyang Medical School, University of South China, Hengyang, 421001, Hunan, People's Republic of China. [email protected].
  • 11 The 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. [email protected].
  • # Contributed equally.
PMID: 41284105 DOI: 10.1007/s11033-025-11191-x
Abstract

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.

Keywords

Irg1-Itaconate axis; Microglia; Microglia polarization; Parkinson's disease; Succinate dehydrogenase.

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