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- W2987814271 endingPage "109618" @default.
- W2987814271 startingPage "109618" @default.
- W2987814271 abstract "Amyloid-β (Aβ) activating the pyroptotic cell pathway has been reported to act as a component in the progression of Alzheimer's disease (AD). As another major pathophysiological protein process in AD, the abnormal hyperphosphorylation of tau proteins exerts neurotoxic effects through a variety of mechanisms. However, data describing the relationship between hyperphosphorylated tau proteins and pyroptosis are very scarce. In this study, we used two hyperphosphorylated tau models, intracerebroventricular (ICV) forskolin (FSK, a PKA activator) rat model and ICV-streptozotocin (STZ) rat model; also, FSK and STZ treated PC12 cells as in vitro models to test the relationship between hyperphosphorylated tau proteins and pyroptosis. We found that FSK and STZ significantly increased the hyperphosphorylated tau level, pyroptosis-related protein in PC12 cell and rats' brain, and inhibited the activity of caspase-1 by caspase-1 inhibitor, caspase-1 siRNA, or incubated with Interleukin(IL)-1β/IL-18 neutralizing antibody could notably alleviate the FSK and STZ induced PC12 cells damage and improve the cognitive disorder in ICV-FSK and ICV-STZ rats. Suppressed the level of hyperphosphorylated tau by LiCl also significantly decreased caspase-1 activity and the content of inflammatory cytokines in FSK or STZ treated PC12 cells. In summary, our results demonstrated that inflammasomes mediated pyroptosis at least one underlying pathogenic mechanism for the neurotoxicity induced by hyperphosphorylated tau in PC12 cells and dementia rats. IL-1β and IL-18, the downstream of caspase-1, in turn increased hyperphosphorylated tau while spreading neuroinflammation." @default.
- W2987814271 created "2019-11-22" @default.
- W2987814271 creator A5011208292 @default.
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- W2987814271 creator A5076559170 @default.
- W2987814271 creator A5081139903 @default.
- W2987814271 creator A5086364425 @default.
- W2987814271 date "2020-01-01" @default.
- W2987814271 modified "2023-09-25" @default.
- W2987814271 title "Interaction between hyperphosphorylated tau and pyroptosis in forskolin and streptozotocin induced AD models" @default.
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- W2987814271 doi "https://doi.org/10.1016/j.biopha.2019.109618" @default.
- W2987814271 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/31731189" @default.
- W2987814271 hasPublicationYear "2020" @default.