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- W2056636618 abstract "The control of translation is disturbed in Alzheimer's disease (AD). This study analysed the crosslink between the up regulation of double-stranded RNA-dependent-protein kinase (PKR) and the down regulation of mammalian target of rapamycin (mTOR) signalling pathways via p53, the protein Regulated in the Development and DNA damage response 1 (Redd1) and the tuberous sclerosis complex (TSC2) factors in two β-amyloid peptide (Aβ) neurotoxicity models. In SH-SY5Y cells, Aβ42 induced an increase of PT451-PKR and of the ratio p66/(p66 + p53) in nuclei and a physical interaction between these proteins. Redd1 gene levels increased and PT1462-TSC2 decreased. These disturbances were earlier in rat primary neurons with nuclear co-localization of Redd1 and PKR. The PKR gene silencing in SH-SY5Y cells prevented these alterations. p53, Redd1 and TSC2 could represent the molecular links between PKR and mTOR in Aβ neurotoxicity. PKR could be a critical target in a therapeutic program of AD." @default.
- W2056636618 created "2016-06-24" @default.
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- W2056636618 date "2009-10-01" @default.
- W2056636618 modified "2023-10-16" @default.
- W2056636618 title "Evidence of molecular links between PKR and mTOR signalling pathways in Aβ neurotoxicity: Role of p53, Redd1 and TSC2" @default.
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- W2056636618 doi "https://doi.org/10.1016/j.nbd.2009.07.004" @default.
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