Thymopentin (TP-5) prevents lipopolysaccharide-induced neuroinflammation and dopaminergic neuron injury by inhibiting the NF-κB/NLRP3 signaling pathway.

Si-Jia Peng, Ya Feng, Xuan Li, Xi-Xi Wang, Yu Wang, Bu-Tian Zhou, Ye Liu, Te Liu, Yun-Cheng Wu

International immunopharmacology 2023 Jun

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Neuroinflammation plays a pivotal role in neurodegenerative diseases, including Parkinson's disease, Alzheimer's disease, amyotrophic lateral sclerosis and stroke, and is accompanied by excessive release of inflammatory cytokines and mediators by activated microglia. Microglial inflammatory response inhibition may be an effective strategy for preventing inflammatory disorders. However, the reciprocal connections between the central nervous system (CNS) and immune system have not been elucidated. Thus far, these links have been proven to mainly involve immuno- and neuropeptides. The pentapeptide thymopentin (TP-5) exerts a significant immunomodulatory effect; however, its antineuroinflammatory effects and underlying mechanism are still unclear. In this study, lipopolysaccharide (LPS) was used to establish an inflammation model, and the therapeutic effect of TP-5 was evaluated. Behavioral tests showed that TP-5 treatment could improve the performance of LPS-treated mice in the open field and pole test, but not hanging wire test. TP-5 also attenuated neuronal lesions in the brains of LPS-treated mice. TP-5 reduced cytotoxicity and morphological changes in activated microglia. Label-free quantitative analysis indicated that the expression of multiple proteins and the activation of associated signaling pathways were altered by TP-5. Moreover, TP-5 could inhibit LPS-induced neuroinflammation in the brain and BV2 microglia and the expression of major genes in the NF-κB/NLRP3 signaling pathway. Additionally, tyrosine hydroxylase (TH) expression downregulation was rescued in the LPS + TP-5 group compared with the LPS group. We conclude that TP-5 exerts neuroprotection by alleviating LPS-induced inflammatory damage and dopaminergic neurodegeneration. The protective effect of TP-5 may involve the NF-κB/NLRP3 signaling pathway. Copyright © 2023. Published by Elsevier B.V.

Citation

Si-Jia Peng, Ya Feng, Xuan Li, Xi-Xi Wang, Yu Wang, Bu-Tian Zhou, Ye Liu, Te Liu, Yun-Cheng Wu. Thymopentin (TP-5) prevents lipopolysaccharide-induced neuroinflammation and dopaminergic neuron injury by inhibiting the NF-κB/NLRP3 signaling pathway. International immunopharmacology. 2023 Jun;119:110109