Title:
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PKR and PP1C polymorphisms in alzheimer’s disease risk
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Author:
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Palomer, Ernest; Ill-Raga, Gerard, 1982-; Tajes Orduña, Marta; Ramos Fernández, Eva, 1984-; Bosch Morató, Mònica, 1986-; Guivernau Almazán, Biuse, 1988-; Galán, José J; Clarimón Echevarría, Jordi; Antúnez, Carmen; Boada, Mercè; Real, Luis M; Fandos, César; Muñoz López, Francisco José, 1964-
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Abstract:
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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. |
Abstract:
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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). |
Subject(s):
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-Alzheimer, Malaltia d' -Alzheimer’s Disease -BACE1 -PKR -PP1 -eIF2α |
Rights:
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© 2011 SciRes
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Document type:
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Article Article - Published version |
Published by:
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Scientific Research Publishing
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