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- W2072912108 abstract "Intracellular accumulation of filamentous tau proteins is a defining feature of neurodegenerative diseases, including Alzheimer's disease (AD), all known collectively as tauopathies. However the pathogenesis of tauopathies remains mostly unknown. Recently it was revealed that tau oligomer levels in cortex of early-staged AD were significantly increased. We have been reporting that endoplasmic reticulum (ER) stress is involved in the onset of AD. Here we show that ER stress increases the tau levels in neurons. SH-SY5Y cells or primary cultured neurons prepared from mice cerebral cortex were incubated for appropriate time in media without glucose or media with tunicamycin or tapsigargin. Cells were lysed at the end of the treatment period and used for immunoblot analysis of tau or phosphorylation of the translation initiation factor eIF2α. Total mRNA also was isolated from the cells for measure of level of tau mRNAs by the TaqMan real-time PCR. The cells were pulse-labeled in media containing 35S-methionine/cystein and chased in media with ER stress. Tau protein levels were significantly elevated in response to ER stress compared with controls in parallel with phosphorylation of eIF2α. There were little apparent differences in tau mRNAs levels between cells with or without ER stress, verifying that ER stress did not increase tau gene transcription or mRNA stability. Moreover there were no apparent differences between the half-lives of tau protein under with and without ER stress, indicating that the tau increase is not due to tau protein stabilization. ER stress may increase tau levels via the protein synthesis steps, which could be initiating molecular mechanism in tauopathies." @default.
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- W2072912108 date "2010-07-01" @default.
- W2072912108 modified "2023-09-27" @default.
- W2072912108 title "P1-360: Endoplasmic reticulum stress increases tau levels" @default.
- W2072912108 doi "https://doi.org/10.1016/j.jalz.2010.05.914" @default.
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