2. Academic Validation
  3. Paraquat induces neuroinflammation through glycolytic reprogramming in microglia: evidence from network toxicology analysis and in vitro experiments

Paraquat induces neuroinflammation through glycolytic reprogramming in microglia: evidence from network toxicology analysis and in vitro experiments

  • Chem Biol Interact. 2026 Jun 1:432:112037. doi: 10.1016/j.cbi.2026.112037.
Yi Yang 1,  Yin Xu 2,  Qingtai Meng 3,  Xinyang Wang 4,  Ya Tian 5,  Liang Lyu 6,  Xiaofeng Zhang 7
Affiliations

Affiliations

  • 1 Department of Toxicology, Public Health School, Harbin Medical University, Harbin, 150081, China. Electronic address: [email protected].
  • 2 Department of Toxicology, Public Health School, Harbin Medical University, Harbin, 150081, China; Shaoxing Center for Disease Control and Prevention, Shaoxing, 312000, China. Electronic address: [email protected].
  • 3 Department of Microbiology, School of Basic Medical Science, Harbin Medical University, Harbin, 150081, China. Electronic address: [email protected].
  • 4 Department of Toxicology, Public Health School, Harbin Medical University, Harbin, 150081, China. Electronic address: [email protected].
  • 5 Department of Toxicology, Public Health School, Harbin Medical University, Harbin, 150081, China. Electronic address: [email protected].
  • 6 Department of Toxicology, Public Health School, Harbin Medical University, Harbin, 150081, China. Electronic address: [email protected].
  • 7 Department of Toxicology, Public Health School, Harbin Medical University, Harbin, 150081, China. Electronic address: [email protected].
PMID: 41839307 DOI: 10.1016/j.cbi.2026.112037
Abstract

Paraquat (PQ) has been strongly linked to Parkinson disease, although the underlying mechanisms remain incompletely defined. Network toxicology analysis was used to predict the possible targets and pathways of PQ neurotoxicity, and BV2 cells were used to validate the predicted results and possible mechanisms through Molecular Biology techniques. The analysis of network toxicology showed that PQ-targeted microglia may be accompanied by glucose metabolism disorder. PQ markedly enhanced glycolysis in BV2 cells, showing an increase of lactate content, the expression level of HK2 and GLUT-1, and glycolytic flux. PQ activated mTOR while inhibiting AMPK, which enhanced glycolysis in microglia and promoted their pro-inflammatory polarization. Notably, inhibiting glycolysis with glucose analogue or silencing hk2 effectively attenuated PQ-induced inflammatory response and Apoptosis of dopaminergic neurons. These findings uncover an unrecognized mechanism by which glycolytic reprogramming in microglia contributes to PQ neurotoxicity through promoting neuroinflammation, highlighting microglial glycolysis as a potential intervention target for environmental toxicants-associated neurodegenerative disorders.

Keywords

Glycolytic reprogramming; Microglia; Network toxicology; Neuroinflammation; Paraquat.

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