1. Ser9p-GSK3β Modulation Contributes to the Protective Effects of Vitamin C in Neuroinflammation.
- Author
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Ruggiero M, Cianciulli A, Calvello R, Porro C, De Nuccio F, Kashyrina M, Miraglia A, Lofrumento DD, and Panaro MA
- Subjects
- Animals, Male, Mice, Cell Line, Disease Models, Animal, Glycogen Synthase Kinase 3 beta metabolism, Lipopolysaccharides, Mice, Inbred C57BL, Microglia drug effects, Microglia metabolism, Parkinson Disease drug therapy, Parkinson Disease metabolism, Phosphorylation drug effects, Serine metabolism, Anti-Inflammatory Agents pharmacology, Ascorbic Acid pharmacology, Neuroinflammatory Diseases drug therapy, Neuroprotective Agents pharmacology
- Abstract
Background: The prolonged activation of microglia and excessive production of pro-inflammatory cytokines can lead to chronic neuroinflammation, which is an important pathological feature of Parkinson's disease (PD). We have previously reported the protective effect of Vitamin C (Vit C) on a mouse model of PD. However, its effect on microglial functions in neuroinflammation remains to be clarified. Glycogen synthase kinase 3β (GSK3β) is a serine/threonine kinase having a role in driving inflammatory responses, making GSK3β inhibitors a promising target for anti-inflammatory research., Methods: In this study, we investigated the possible involvement of GSK3β in Vit C neuroprotective effects by using a well-known 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced animal model of PD and a cellular model of neuroinflammation, represented by Lipopolysaccharide (LPS)-activated BV-2 microglial cells., Results: We demonstrated the ability of Vit C to decrease the expression of different mediators involved in the inflammatory responses, such as TLR4, p-IKBα, and the phosphorylated forms of p38 and AKT. In addition, we demonstrated for the first time that Vit C promotes the GSK3β inhibition by stimulating its phosphorylation at Ser9., Conclusion: This study evidenced that Vit C exerts an anti-inflammatory function in microglia, promoting the upregulation of the M2 phenotype through the activation of the Wnt/β-catenin signaling pathway.
- Published
- 2024
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