PKR and PP1C polymorphisms in alzheimer’s disease risk

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• dc.contributor.author Palomer, Ernestca
• dc.contributor.author Ill-Raga, Gerard, 1982-ca
• dc.contributor.author Tajes Orduña, Martaca
• dc.contributor.author Ramos Fernández, Eva, 1984-ca
• dc.contributor.author Bosch Morató, Mònica, 1986-ca
• dc.contributor.author Guivernau Almazán, Biuse, 1988-ca
• dc.contributor.author Galán, José Jca
• dc.contributor.author Clarimón Echevarría, Jordica
• dc.contributor.author Antúnez, Carmenca
• dc.contributor.author Boada, Mercèca
• dc.contributor.author Real, Luis Mca
• dc.contributor.author Fandos, Césarca
• dc.contributor.author Muñoz López, Francisco José, 1964-ca
• dc.date.accessioned 2016-04-20T17:41:46Z
• dc.date.available 2016-04-20T17:41:46Z
• dc.date.issued 2011
• dc.description.abstract Alzheimer’s disease (AD) is a neurodegenerative disease characterized by senile plaques and neurofibrillary tangles. Senile plaques are deposits of amyloid ß-peptide (Aß) produced by the cleavage of a transmembrane protein termed Amyloid Precursor Protein (APP). The amyloidogenic cleavage of APP is performed by γ-secretase complex and ß-site APP cleaving enzyme 1 (BACE1), a key enzyme in AD that can be activated by different noxious stimuli. Interestingly, some viruses could activate double-stranded RNA-activated protein kinase (PKR), which phosphorylates Eukaryotic Initiation Factor 2 alpha (eIF2α). This phosphorylation stops global translation to avoid any synthesis of viral infective proteins, but paradoxically up-regulates BACE1 translation. One of the viral mechanisms to circumvent eIF2α phosphorylation is the recruitment of protein phosphatase 1 (PP1), to fully dephosphorylate eIF2α and allow viral protein synthesis. Due to the functional relationship between BACE1, PKR, PP1 and AD we have performed a large (1122 cases and 1191 control individuals) case-control genetic analysis using two biallelic polymorphisms rs2254958 and rs7480390, located within the genes coding for PKR and the catalytic unit A of PP1, respectively. Although a trend to association of the rs2254958 TT genotype with AD risk was found, our results show that neither rs7480390 nor rs2254958 are associated with AD susceptibility.ca
• dc.description.sponsorship This work was supported by the Spanish Ministerio de Ciencia y Tecnología (FIS: PI07/0593 and PI10/00587; ISCIII-RETIC RED HERACLES RD06/0009/002- FEDER).
• dc.format.mimetype application/pdfca
• dc.identifier.citation Palomer E, Ill-Raga G, Tajes M, Ramos-Frnández E, Bosch-Morató M, Guivernau B et al. PKR and PP1C polymorphisms in alzheimer’s disease risk. Neuroscience & Medicine. 2011;2(3):226-31. DOI: 10.4236/nm.2011.23031ca
• dc.identifier.doi http://dx.doi.org/10.4236/nm.2011.23031
• dc.identifier.issn 2158-2912
• dc.identifier.uri http://hdl.handle.net/10230/26137
• dc.language.iso engca
• dc.publisher Scientific Research Publishingca
• dc.relation.ispartof Neuroscience & Medicine. 2011;2(3):226-31
• dc.rights © 2011 SciResca
• dc.rights.accessRights info:eu-repo/semantics/openAccessca
• dc.subject.keyword Alzheimer’s Disease
• dc.subject.keyword BACE1
• dc.subject.keyword PKR
• dc.subject.keyword PP1
• dc.subject.keyword eIF2α
• dc.subject.other Alzheimer, Malaltia d'ca
• dc.title PKR and PP1C polymorphisms in alzheimer’s disease riskca
• dc.type info:eu-repo/semantics/articleca
• dc.type.version info:eu-repo/semantics/publishedVersionca