Abstract
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 language | English (US) |
|---|---|
| Article number | 1046992 |
| Journal | Frontiers in Molecular Neuroscience |
| Volume | 15 |
| DOIs | |
| State | Published - 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.
Keywords
- Galectin-9
- Parkinson’s disease
- mitochondrial dysfunction
- neurodegenerative diseases
- neuroinflammation
PubMed: MeSH publication types
- Journal Article