TALEN Editing of APP Gene in WiCell WA09 (H9) Cells to directly express amyloid beta proteins
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ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE119527 | GEO | 2018/12/31
REPOSITORIES: GEO
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Project description:TALEN Editing of APP Gene in WiCell WA09 (H9) Cells to directly express amyloid beta proteins
| PRJNA489467 | ENA
Project description:Abnormal metal accumulation is associated with Alzheimer’s disease (AD) and has a relevant role in affecting amyloid beta-peptide (Abeta) aggregation and neurotoxicity.In the present study, employing a microarray analysis of 35,129 genes, we analyzed gene expression profile changes due to exposure to Abeta-Zn or Abeta-Cu complexes in neuronal-like cells (SH-SY5Y). Microarray data indicated that Abeta-Zn or Abeta-Cu complexes selectively alter expression of genes mainly related to cell death, inflammatory responses, and apoptosis.Taken together these findings indicate that Abeta-Zn or Abeta-Cu show some commonalities in affecting AD-related target functions. The overall modulatory activity on these genes supports the idea of a possible net result leading to mechanisms that counteract toxic effects of Abeta-Zn or Abeta-Cu.
2012-05-01 | GSE37661 | GEO
Project description:We combined a mouse model of Abeta accumulation and transcriptomics, and identified Klc1 as an Abeta accumulation modifier in vivo.
2014-01-15 | GSE40330 | GEO
Project description:Amyloid-beta peptides which aggregate and accumulate in Alzheimer’s disease (AD) brain are known to have sequential N-terminal truncations and multiple post-translational modifications (PTM) such as isomerization, pyroglutamate formation, phosphorylation, nitration and dityrosine cross-linking. Here we add to the list of PTM citrullination (deimination) of Arg5 residue in plaque-derived Abeta in sporadic AD brains, identified by tandem mass spectrometry. We quantitated the level of citrullination on multiple N-truncated Abeta isoforms present in plaque-associated fractions and found that almost 30 % of pyroGlu3-Abeta pool was citrullinated in plaques from AD temporal cortex. We also documented citrullinated Abeta peptides in the detergent insoluble fractions from AD frontal cortex with ~ 22 % citrullination in the pyroGlu3-Abeta pool. Citrullination of Abeta is a common PTM, closely associated with pyroglutamate-Abeta formation and Abeta accumulation in AD. This may have implications for Abeta toxicity, auto-antigenicity of Abeta, and may be relevant for the design of diagnostic assays and therapeutic targeting.
2021-11-24 | PXD025620 | Pride
Project description:We combined a mouse model of Abeta accumulation and transcriptomics, and identified Klc1 as an Abeta accumulation modifier in vivo. For this transcriptomics analysis, we used 12 arrays (one mouse mRNA sample per array) for inbred mice analyses and 28 arrays for the APP Tg mice of mixed genetic backgrounds. First, 13309 probes whose signals were reliably detectable in all 40 arrays were selected from 25967 probes on the Illumina mouse Ref-8 Expression BeadChip. Second, to select the probes whose expression levels were affected by the DBA genetic background, we compared the expression levels of the 13309 probes in DBA, B6 and SJL inbred (non-Tg) mice (unpaired t-test).M-cM-^@M-^@Using inbred mice means that any change in gene expression is based on their genetic background, not the secondary effects of Abeta accumulation. To minimize the chance of false positives, we applied strict criteria in this selection: the fold change was equal to or more than 1.5 and the false discovery rate (FDR) was set to 0.001. In total 54 probes were identified, with the signals of 47 probes being lower and 7 probes being higher in DBA mice than those in either B6 or SJL. In the final step, we examined the correlation between the expression levels of these 54 probes and Abeta40 levels in the GuHCl fraction in APP Tg mice. Using strict selection criteria (PearsonM-bM-^@M-^Ys product-moment correlation FDR=0.001), we identified a total of four probes which correlated with Abeta levels. Two of these probes were higher in DBA and negatively correlated with the levels of Abeta accumulation. The other two probes were lower in DBA and positively correlated with the levels of Abeta accumulatio. Notably, the two probes (probe ID 4050133 and 6130468) that positively correlated with Abeta accumulation both detected the same transcript: kinesin light chain 1 (Klc1; also known as Kns2).
2014-01-15 | E-GEOD-40330 | biostudies-arrayexpress
Project description:Oligomeric forms of amyloid-beta peptide (Abeta) are presumed to play a pivotal role in the pathogenesis of Alzheimer’s disease (AD). However, it is still unclear how Abeta oligomers contribute to AD pathogenesis in patient neural cells. We generated induced pluripotent stem cells (iPSCs) from a familial AD patient and differentiated them into neural cells. Abeta oligomers were accumulated in neural cells of AD bearing amyloid precursor protein (APP)-E693delta mutation. To uncover Abeta oligomers in AD(APP-E693delta) neural cells, we analyzed gene expression profiles of control and the AD neural cells
2013-03-22 | GSE43326 | GEO
Project description:Transgenic animals were engineered to express human amyloid peptide controlled by a muscle-specific, heat-inducible promoter. At low temperatures (16°C) Abeta expression is minimal, while at higher temperatures (20-25°C) Abeta accummulates in large quantities and causes paralysis. GFP- and GFP::degron (a toxic aggregating GFP mutant)-expressing animals were used as controls. Animals were grown at 16°C till early 3rd larval stage and then upshifted to 25°C. Animals were harvested at the time of upshift (T0), and every 4 hours later until 20 hours postupshift (T4-T20).
2015-02-12 | E-GEOD-65851 | biostudies-arrayexpress
Project description:Transgenic animals were engineered to express human amyloid peptide controlled by a muscle-specific, heat-inducible promoter. At low temperatures (16°C) Abeta expression is minimal, while at higher temperatures (20-25°C) Abeta accummulates in large quantities and causes paralysis. GFP- and GFP::degron (a toxic aggregating GFP mutant)-expressing animals were used as controls.
2015-02-12 | GSE65851 | GEO
Project description: Not available
| S-EPMC4770288 | biostudies-other
Project description:Extracellular senile plaques of amyloid beta (Abeta) are a pathological hallmark in brain of patients with Alzheimer`s Disease (AD). Abeta is generated by the amyloidogenic processing of the amyloid precursor protein (APP). Concomitant to Abeta load, AD brain is characterized by an increase in protein level and activity of the angiotensin-converting enzyme (ACE). ACE inhibitors are a widely used class of drugs with established benefits for patients with cardiovascular disease. However, the role of ACE and ACE inhibition in the development of Abeta plaques and the process of AD-related neurodegeneration is not clear since ACE was reported to degrade Abeta. To investigate the effect of ACE inhibition on AD-related pathomechanisms, we used Tg2576 mice with neuron-specific expression of APPSwe as AD model. From 12 months of age, substantial Abeta plaque load accumulates in the hippocampus of Tg2576 mice as a brain region, which is highly vulnerable to AD-related neurodegeneration. The effect of central ACE inhibition was studied by treatment of 12 month-old Tg2576 mice for six months with the brain penetrating ACE inhibitor captopril. At an age of 18 months, hippocampal gene expression profiling was performed of captopril-treated Tg2576 mice relative to untreated 18 month-old Tg2576 controls with high Abeta plaque load. As an additional control, we used 12 month-old Tg2576 mice with low Abeta plaque load. Whole genome microarray gene expression profiling revealed gene expression changes induced by the brain-penetrating ACE inhibitor captopril, which could reflect the neuro-regenerative potential of central ACE inhibition. Microarray gene expression profiling was performed of hippocampi isolated from aged, 18 month-old Tg2576 (APPSwe-transgenic) AD mice with high Abeta plaque load relative to age-matched Tg2576 mice, which were treated for 6 months with the centrally active ACE inhibitor captopril. Another study group consisted of 12 month-old Tg2576 mice with low Abeta plaque load. In total, three study groups were analyzed, i.e. (i) 18 month-old untreated Tg2576 mice with high Abeta plaque load, (ii) age-matched Tg2576 mice treated for 6 months with the brain-penetrating ACE inhibitor captopril (20 mg/kg body weight/day in drinking water), and (iii) untreated 12 month-old Tg2576 mice with low Abeta plaque load reflecting the time point when captopril treatment was initiated. Two biological replicates were made of each group, and total hippocampal RNA of four mice was pooled for one gene chip.
2013-05-14 | E-GEOD-46871 | biostudies-arrayexpress