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MST4 Regulates Microglia Neuroinflammation via Targeting PKM2 Nuclear Translocation in Epilepsy: An In Vivo and In
Jie Fu1, Shaotao Zhang2, Yifei Chu3
1Department of Neurology, the Affiliated Hospital of Southwest Medical University, Taiping Street, Jiangyang District, Luzhou, 646000, China. fujessie@swmu.edu.cn.
Neurochemical Research
|July 4, 2026
Summary
Mammalian sterile-20-like kinase 4 (MST4) reduces neuroinflammation in epilepsy by inhibiting PKM2 nuclear translocation. This finding offers a potential therapeutic target for epilepsy treatment.
Area of Science:
- Neuroscience
- Inflammation Research
- Epilepsy Pathogenesis
Background:
- Microglia-driven neuroinflammation is a key factor in epilepsy development.
- Mammalian sterile-20-like kinase 4 (MST4) is implicated in inflammatory processes, but its role in epilepsy-related neuroinflammation is unknown.
Purpose of the Study:
- To investigate the effect of MST4 on microglia-mediated neuroinflammation in epilepsy.
- To elucidate the underlying molecular mechanisms involving MST4 in epilepsy.
Main Methods:
- Established a pilocarpine-induced rat epilepsy model and lipopolysaccharide (LPS)-stimulated microglia model.
- Utilized lentivirus for MST4 knockdown/overexpression, EEG for brain activity, western blot/qRT-PCR for gene/protein expression, immunofluorescence, TUNEL staining, and Co-IP assay.
- Investigated the interaction between MST4 and PKM2 and its effect on PKM2 nuclear translocation.
Main Results:
- MST4 and nuclear PKM2 expression increased in epileptic rats and co-localized with microglia.
- MST4 overexpression suppressed microglia activation, reduced TNF-α and IL-1β release, and decreased neuronal apoptosis.
- MST4 interacted with PKM2, inhibiting its nuclear translocation; blocking PKM2 nuclear translocation reversed MST4 knockdown-induced neuroinflammation.
Conclusions:
- MST4 alleviates microglia-mediated neuroinflammation in epilepsy.
- MST4's anti-neuroinflammatory mechanism involves the inhibition of PKM2 nuclear translocation.
