Er of genes that together would make up the functionalityBergen etEr of genes that together

Er of genes that together would make up the functionalityBergen et
Er of genes that together would make up the functionalityBergen et al. BMC Genomics (2015) 16:Page 8 ofFig. 3 Upregulation of the over-represented unfolded protein response in AD affected CPE. In the schematic drawing all regulated potential molecular ABT-737MedChemExpress ABT-737 players of the unfolded protein response are presented. The filled (red) symbols represent the entries which are actually statistically significantly upregulated in AD affected CPE (Br5?) in our data set(s). Other entries may also be expressed by the CPE, but are not regulated between healthy and AD-affected CPEproteins. Affected neurons activate a number of protective mechanisms, such as the unfolded protein response [44], perhaps nonsense mediated RNA decay, as well as the ER-integrated stress response (ISR) [45] and the protein ubiquitin pathway [46]. In early stages of AD, the ISR temporarily decreases protein synthesis via the PubMed ID:https://www.ncbi.nlm.nih.gov/pubmed/28388412 phosphorylationof eIF-2-alpha to reduce the overall protein load in the cell [45]. Nonetheless, prolonged stress may lead to reduction in the translation of cellular protein and, consequently, neural dysfunction and neurodegenerative disease. Obviously, the CPE is a neuro-epithelium with multiple receptors but, unlike neurons does not have axons,Bergen et al. BMC Genomics (2015) 16:Page 9 ofFig. 4 (See legend on next page.)Bergen et al. BMC Genomics (2015) 16:Page 10 of(See figure on previous page.) Fig. 4 Cluster analysis of mean expression values for the down-regulated genes in AD (Br5?) choroid plexus compared to healthy control choroid plexus (Br0?). Cluster analysis was performed using GENE-E (version 3.0.204; analysis performed on 10/10/2015) with “one minus Pearson correlation” and “Average linkage method” http://www.broadinstitute.org/cancer/software/GENE-E/. On the Y-axis the gene symbols are shown, on the X-axis the individual samples. Blue and red colors indicate, respectively relatively low and high numerical expression values. The dendograms at the top and the left side denote the (close) relationships between, respectively, the samples and the genes. Analysis parameter values are given below the figure. Both the AD and control samples cluster nicely together. To view details, please use your PDF zoom function.dendrites or synapses. However, by similarity, we hypothesize that, in AD, A induced prolonged oxidative stress impairs the major functions of the CPE (production and sink of the CSF, para-cellular transport over the BCSFB and peripheral immune cell recruitment).BSCFB integrity may be compromised in AD-affected CPEWe found that RNA expression of CLDN5 was downregulated in the AD-affected CPE cells. We confirmed the much lower presence of CLDN-5 protein in AD- affected CPE by immunohistochemistry (Fig. 5). Please note that the observed absence of CLDN5 protein mayTable 2 Validation of microarray analysis by RT-PCR (three independent repeats) of 17 selected genesRT-PCR#1 Gene AGXT2L1 SPP1 ITGAV ZBTB1 IFRD1 IER5 ARMET LPIN1 PubMed ID:https://www.ncbi.nlm.nih.gov/pubmed/26740125 DNAJA4 ATF4 DLC1 ANXA5 EPHX2 KCNJ13 CIRBP CLDN5 LYPLAL1 PRDMbRT-PCR#2 P value 0.003 0.004 0.004 0.022 0.731 0.002 0.051 0.002 0.038 0.038 0.004 0.001 0.002 0.001 0.004 0.002 0.001 0.002 0.002 1.81 4.58 2.94 2.25 4.63 2.56 3.47 -3.15 -2.28 -2.56 -7.12 -5.49 -3.81 -4.17 0.007 0.002 0.001 0.011 0.011 0.002 0.002 0.001 0.001 0.007 0.001 0.001 0.001 0.001 F.C. 17.36 6.59 3.20 7.22 P value 0.010 0.002 0.026 0.RT-PCR#3 F.C. 15.57 8.09 3.33 3.51 P value 0.005 0.001 0.011 0.RT-PCR Mean F.C. 18.04 6.87 3.25 4.30 1.Microarray Mean F.C.a.