Galectin-9/Tim-3 pathway mediates dopaminergic neurodegeneration in MPTP-induced mouse model of Parkinson’s disease

Qinyu Peng, Guoxin Zhang, Xiaodi Guo, Lijun Dai, Min Xiong, Zhaohui Zhang, Liam Chen, Zhentao Zhang

Research output: Contribution to journalArticlepeer-review


Galectin-9 (Gal-9) is a crucial immunoregulatory mediator in the central nervous system. Microglial activation and neuroinflammation play a key role in the degeneration of dopaminergic neurons in the substantia nigra (SN) in Parkinson’s disease (PD). However, it remains unknown whether Gal-9 is involved in the pathogenesis of PD. We found that MPP+ treatment promoted the expression of Gal-9 and pro-inflammatory cytokines (IL-6, IL-1β, TNF-α, and MIP-1α) in a concentration-dependent manner in BV2 cells. Gal-9 enhanced neurodegeneration and oxidative stress induced by MPP+ in SH-SY5Y cells and primary neurons. Importantly, deletion of Gal-9 or blockade of Tim-3 ameliorated microglial activation, reduced dopaminergic neuronal loss, and improved motor performance in an MPTP-induced mouse model of PD. These observations demonstrate a pathogenic role of the Gal-9/Tim-3 pathway in exacerbating microglial activation, neuroinflammation, oxidative stress, and dopaminergic neurodegeneration in the pathogenesis of PD.

Original languageEnglish (US)
Article number1046992
JournalFrontiers in Molecular Neuroscience
StatePublished - Nov 21 2022

Bibliographical note

Funding Information:
This work was supported by grants from the National Key Research & Development Program of China (2019YFE0115900), the National Natural Science Foundation of China (nos. 81771382 and 81822016), and the Medical Science Advancement Program of Wuhan University, grant (TFLC2018001).

Publisher Copyright:
Copyright © 2022 Peng, Zhang, Guo, Dai, Xiong, Zhang, Chen and Zhang.


  • Galectin-9
  • Parkinson’s disease
  • mitochondrial dysfunction
  • neurodegenerative diseases
  • neuroinflammation

PubMed: MeSH publication types

  • Journal Article


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