Evidence of molecular links between PKR and mTOR signalling pathways in Aβ neurotoxicity: Role of p53, Redd1 and TSC2

Evidence of molecular links between PKR and mTOR signalling pathways in Aβ neurotoxicity: Role of p53, Redd1 and TSC2

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 Regulat...

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Main Authors: Milena Morel, Julien Couturier, Raymond Pontcharraud, Roger Gil, Bernard Fauconneau, Marc Paccalin, Guylène Page
Format: Article
Language:English
Published: Elsevier 2009-10-01
Series:Neurobiology of Disease
Subjects:
Alzheimer's disease
PKR
p53
Redd1
TSC2
mTOR
Online Access:http://www.sciencedirect.com/science/article/pii/S0969996109001776
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spelling doaj-bdfd3f9578d541eb979c9dcefb94538b2021-03-20T04:57:57ZengElsevierNeurobiology of Disease1095-953X2009-10-01361151161Evidence of molecular links between PKR and mTOR signalling pathways in Aβ neurotoxicity: Role of p53, Redd1 and TSC2Milena Morel0Julien Couturier1Raymond Pontcharraud2Roger Gil3Bernard Fauconneau4Marc Paccalin5Guylène Page6Research Group on Brain Aging, GReViC EA 3808, University of Poitiers, 6 rue de la Milétrie BP 199, 86034 Poitiers Cedex, FranceResearch Group on Brain Aging, GReViC EA 3808, University of Poitiers, 6 rue de la Milétrie BP 199, 86034 Poitiers Cedex, FranceResearch Group on Brain Aging, GReViC EA 3808, University of Poitiers, 6 rue de la Milétrie BP 199, 86034 Poitiers Cedex, FranceResearch Group on Brain Aging, GReViC EA 3808, University of Poitiers, 6 rue de la Milétrie BP 199, 86034 Poitiers Cedex, France; Department of Neurology, Poitiers University Hospital, 2 rue de la Milétrie, 86000 Poitiers Cedex, FranceResearch Group on Brain Aging, GReViC EA 3808, University of Poitiers, 6 rue de la Milétrie BP 199, 86034 Poitiers Cedex, FranceResearch Group on Brain Aging, GReViC EA 3808, University of Poitiers, 6 rue de la Milétrie BP 199, 86034 Poitiers Cedex, France; Department of Geriatrics, Poitiers University Hospital, 2 rue de la Milétrie, 86000 Poitiers Cedex, FranceResearch Group on Brain Aging, GReViC EA 3808, University of Poitiers, 6 rue de la Milétrie BP 199, 86034 Poitiers Cedex, France; Corresponding author. Fax: +33 5 49 36 62 63.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.http://www.sciencedirect.com/science/article/pii/S0969996109001776Alzheimer's diseasePKRp53Redd1TSC2mTOR
collection DOAJ
language English
format Article
sources DOAJ
author Milena Morel
Julien Couturier
Raymond Pontcharraud
Roger Gil
Bernard Fauconneau
Marc Paccalin
Guylène Page
spellingShingle Milena Morel
Julien Couturier
Raymond Pontcharraud
Roger Gil
Bernard Fauconneau
Marc Paccalin
Guylène Page
Evidence of molecular links between PKR and mTOR signalling pathways in Aβ neurotoxicity: Role of p53, Redd1 and TSC2
Neurobiology of Disease
Alzheimer's disease
PKR
p53
Redd1
TSC2
mTOR
author_facet Milena Morel
Julien Couturier
Raymond Pontcharraud
Roger Gil
Bernard Fauconneau
Marc Paccalin
Guylène Page
author_sort Milena Morel
title Evidence of molecular links between PKR and mTOR signalling pathways in Aβ neurotoxicity: Role of p53, Redd1 and TSC2
title_short Evidence of molecular links between PKR and mTOR signalling pathways in Aβ neurotoxicity: Role of p53, Redd1 and TSC2
title_full Evidence of molecular links between PKR and mTOR signalling pathways in Aβ neurotoxicity: Role of p53, Redd1 and TSC2
title_fullStr Evidence of molecular links between PKR and mTOR signalling pathways in Aβ neurotoxicity: Role of p53, Redd1 and TSC2
title_full_unstemmed Evidence of molecular links between PKR and mTOR signalling pathways in Aβ neurotoxicity: Role of p53, Redd1 and TSC2
title_sort evidence of molecular links between pkr and mtor signalling pathways in aβ neurotoxicity: role of p53, redd1 and tsc2
publisher Elsevier
series Neurobiology of Disease
issn 1095-953X
publishDate 2009-10-01
description 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.
topic Alzheimer's disease
PKR
p53
Redd1
TSC2
mTOR
url http://www.sciencedirect.com/science/article/pii/S0969996109001776
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