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• W1986401878 startingPage "25" @default.
• W1986401878 abstract "Amyloid-<TEX>${beta}$</TEX>-peptide (<TEX>$A{beta}$</TEX>) is important in the pathogenesis of Alzheimer's disease (AD). Calpain (<TEX>$Ca^{2+}$</TEX>-dependent protease) and caspase-8 (the initiating caspase for the extrinsic, receptor-mediated apoptosis pathway) have been implicated in <TEX>$AD/A{beta}$</TEX> toxicity. We found that <TEX>$A{beta}$</TEX> promoted degradation of calpastatin (the specific endogenous calpain inhibitor); calpastatin degradation was prevented by inhibitors of either calpain or caspase-8. The results implied a cross-talk between the two proteases and suggested that one protease was responsible for the activity of the other one. In neuron-like differentiated PC12 cells, calpain promotes active caspase-8 formation from procaspase-8 via the <TEX>$A{beta}$</TEX> and CD95 pathways, along with degradation of the procaspase-8 processing inhibitor caspase-8 (FLICE)-like inhibitory protein, short isoform (FLIPS). Inhibition of calpain (by pharmacological inhibitors and by overexpression of calpastatin) prevents the cleavage of procaspase-8 to mature, active caspase-8, and inhibits FLIPS degradation in the <TEX>$A{beta}$</TEX>-treated and CD95-triggered cells. Increased cellular Ca2+ per se results in calpain activation but does not lead to caspase-8 activation or FLIPS degradation. The results suggest that procaspase-8 and FLIPS association with cell membrane receptor complexes is required for calpain-induced caspase-8 activation. The results presented here add to the understanding of the roles of calpain, caspase- 8, and CD95 pathway in <TEX>$AD/A{beta}$</TEX> toxicity. Calpain-promoted activation of caspase-8 may have implications for other types of CD95-induced cell damage, and for nonapoptotic functions of caspase-8. Inhibition of calpain may be useful for modulating certain caspase-8-dependent processes." @default.
• W1986401878 created "2016-06-24" @default.
• W1986401878 creator A5016400438 @default.
• W1986401878 date "2014-03-30" @default.
• W1986401878 modified "2023-09-23" @default.
• W1986401878 title "A Correlative Study on Aβ and CD95 Pathway Independent to Ca2+Dependent Protease and Activation of Caspase Activation" @default.
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• W1986401878 doi "https://doi.org/10.13160/ricns.2014.7.1.25" @default.
• W1986401878 hasPublicationYear "2014" @default.
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