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- Farnsworth, B., et al.
(författare)
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Gene Expression of Quaking in Sporadic Alzheimer's Disease Patients is Both Upregulated and Related to Expression Levels of Genes Involved in Amyloid Plaque and Neurofibrillary Tangle Formation
- 2016
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Ingår i: Journal of Alzheimers Disease. - : IOS Press. - 1387-2877 .- 1875-8908. ; 53:1, s. 209-219
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Tidskriftsartikel (refereegranskat)abstract
- Quaking (QKI) is a gene exclusively expressed within glial cells. QKI has previously been implicated in various neurological disorders and diseases, including Alzheimer's disease (AD), a condition for which increasing evidence suggests a central role of glia cells. The objective of the present study was to investigate the expression levels of QKI and three QKI isoforms (QKI5, QKI6, and QKI7) in AD. Genes that have previously been related to the ontogeny and progression of AD, specifically APP, PSEN1, PSEN2, and MAPT, were also investigated. A real-time PCR assay of 123 samples from human postmortem sporadic AD patients and control brains was performed. The expression values were analyzed with an analysis of covariance model and subsequent multiple regressions to explore the possibility of related expression values between QKI, QKI isoforms, and AD-related genes. Further, the sequences of AD-related genes were analyzed for the presence of QKI binding domains. QKI and all measured QKI isoforms were found to be significantly upregulated in AD samples, relative to control samples. However, APP, PSEN1, PSEN2, and MAPT were not found to be significantly different. QKI and QKI isoforms were found to be predictive for the variance of APP, PSEN1, PSEN2, and MAPT, and putative QKI binding sites suggests an interaction with QKI. Overall, these results implicate a possible role of QKI in AD, although the exact mechanism by which this occurs remains to be uncovered.
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2. |
- Farnsworth, B., 1987-, et al.
(författare)
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QKI6B mRNA levels are upregulated in schizophrenia and predict GFAP expression
- 2017
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Ingår i: Brain Research. - : Elsevier BV. - 0006-8993 .- 1872-6240. ; 1669, s. 63-68
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Tidskriftsartikel (refereegranskat)abstract
- Schizophrenia is a highly heritable disorder with a heterogeneous symptomatology. Research increasingly indicates the importance of the crucial and often overlooked glial perturbations within schizophrenia. Within this study, we examined an isoform of quaking (a gene encoding an RNA-binding protein that is exclusively expressed in glial cells), known as QKI6B, and a prototypical astrocyte marker, glial fibrillary acidic protein (GFAP), postulated to be under the regulation of QKI. The expression levels of these genes were quantified across post-mortem brain samples from 55 schizophrenic individuals, and 55 healthy controls, using real-time PCR. We report, through an analysis of covariance (ANCOVA) model, an upregulation of both QKI6B, and GFAP in the prefrontal cortex of brain samples of schizophrenic individuals, as compared to control samples. Previous research has suggested that the QKI protein directly regulates the expression of several genes through interaction with a motif in the target's sequence, termed the Quaking Response Element (QRE). We therefore examined if QICI6B expression can predict the outcome of GFAP, and several oligodendrocyte-related genes, using a multiple linear regression approach. We found that QKI6B significantly predicts the expression of GFAP, but does not predict oligodendrocyte-related gene outcome, as previously seen with other QKI isoforms.
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