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- W2044164680 abstract "In addition to their original applications for lowering cholesterol, statins display multiple neuroprotective effects. Inflammatory reactions and the PI3K/AKT/caspase 3 pathway are strongly implicated in dopaminergic neuronal death in Parkinson's disease (PD). This study aims to investigate how simvastatin affects 6-hydroxydopamine-lesioned PC12 via regulating PI3K/AKT/caspase 3 and modulating inflammatory mediators.6-hydroxydopamine-treated PC12 cells were used to investigate the neuroprotection of simvastatin, its association with the PI3K/AKT/caspase 3 pathway, and antiinflammatory responses. Dopamine transporters (DAT) and tyrosine hydroxylase (TH) were examined in 6-hydroxydopamine-treated PC12 after simvastatin treatment.Simvastatin-mediated neuroprotection was associated with a robust reduction in the upregulation induced by 6-OHDA of inflammatory mediators including IL-6, COX2, and TNF-α. The downregulated DAT and TH levels in 6-OHDA-lesioned PC12 were restored after simvastatin treatment. Simvastatin reversed 6-OHDA-induced downregulation of PI3K/Akt phosphorylation and attenuated 6-OHDA-induced upregulation of caspase 3 in PC12. Furthermore, the PI3K inhibitor LY294002 pronouncedly abolished the simvastatin-mediated attenuation in caspase 3.Our results demonstrate that simvastatin provides robust neuroprotection against dopaminergic neurodegeneration, partially via antiinflammatory mechanisms and the PI3K/Akt/caspase 3 pathway. These findings contribute to a better understanding of the critical roles of simvastatin in treating PD and might elucidate the molecular mechanisms of simvastatin effects in PD." @default.
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- W2044164680 date "2012-12-28" @default.
- W2044164680 modified "2023-10-12" @default.
- W2044164680 title "Simvastatin Induces Neuroprotection in 6-OHDA-Lesioned PC12 via the PI3K/AKT/Caspase 3 Pathway and Anti-Inflammatory Responses" @default.
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- W2044164680 doi "https://doi.org/10.1111/cns.12053" @default.
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