Browse
Submit Data
Databases
API
Help

Metabolomics,Unknown,Transcriptomics,Genomics,Proteomics

Dataset Information

13 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Analysis of gene expression changes in amyloid-beta (ADDL) and CAT-SKL antioxidant treated primary rat neuronal cells

ABSTRACT: Amyloid-beta (Aβ)-induced neurotoxicity is a major contributor to the pathologies associated with Alzheimer’s disease (AD). The formation of reactive oxygen species (ROS), and early response induced by the Aβ peptide, plays a significant role in effecting cellular pathogenesis. Here we apply a particularly effective form of exogenous Aβ, i.e., amyloid beta-derived diffusible ligands (ADDLs), to cultured primary cortical/hippocampal neurons to elicit ROS and drive cellular dysfunction. To prevent and even reverse such effects, we employed a cell-penetrating, peroxisome-targeted, protein biologic - called CAT-SKL. We show the recombinant enzyme enters neurons, reverses Aβ-induced oxidative stress, and increases cell viability. Dramatic restorative effects on damaged neuronal processes were also observed. CAT-SKL, a targeted antioxidant, may represent a new therapeutic approach for treatment disorders, like Alzheimer’s disease, where oxidative stress is manifest. Preclinical testing is warranted and ongoing Primary Rat E18 coritical/hippocampal neurons (derived from Sprague Dawley E18 cortical/hippocampus tissue obtained from BrainBits®, Springfield, IL) were treated with ADDLs in the presence or absence of the targeted antioxidant CAT-SKL to investigate genes that displayed altered expression in response to treatmetns total RNA was isolated and analyzed in an Agilent two-color experiment. Two biological replicates of each condition were directly compared, ratios are treated relative to control (untreated)

ORGANISM(S): Rattus norvegicus

SUBMITTER: Aliccia Bollig-Fischer

PROVIDER: E-GEOD-55369 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

ACCESS DATA

Json Xml

Similar Datasets

Analysis of gene expression changes in amyloid-beta (ADDL) and CAT-SKL antioxidant treated primary rat neuronal cells

Project description:Amyloid-beta (Aβ)-induced neurotoxicity is a major contributor to the pathologies associated with Alzheimer’s disease (AD). The formation of reactive oxygen species (ROS), and early response induced by the Aβ peptide, plays a significant role in effecting cellular pathogenesis. Here we apply a particularly effective form of exogenous Aβ, i.e., amyloid beta-derived diffusible ligands (ADDLs), to cultured primary cortical/hippocampal neurons to elicit ROS and drive cellular dysfunction. To prevent and even reverse such effects, we employed a cell-penetrating, peroxisome-targeted, protein biologic - called CAT-SKL. We show the recombinant enzyme enters neurons, reverses Aβ-induced oxidative stress, and increases cell viability. Dramatic restorative effects on damaged neuronal processes were also observed. CAT-SKL, a targeted antioxidant, may represent a new therapeutic approach for treatment disorders, like Alzheimer’s disease, where oxidative stress is manifest. Preclinical testing is warranted and ongoing

2014-04-11 | GSE55369 | GEO

Mouse hippocampus LC/MS with TMT labeling

Project description:Transgenic mouse models have been widely used to investigate the pathology of Alzheimer’s disease (AD). To elucidate underlying mechanisms of AD pathogenesis by amyloid beta (Aβ) and tau, we have generated a novel animal model of AD; ADLP - APT mice (Alzheimer’s Disease-Like Pathology) – carrying mutations of human amyloid precursor protein (APP), human presenilin-1 (PS1) and human tau. We profiled 9,824 proteins in the hippocampus of ADLP model mice using quantitative proteomics. To identify functional signatures in pathology of ADLP - APT mice, in-depth bioinformatics analysis was performed. For a longitudinal change of differentially expressed proteins (DEPs), we identified ADLP - APT mice hippocampal proteome in an age-dependent manner. Network maps of interactome between Aβ and tau in newly generated ADLP - APT mice reveal relationship between accelerated NFT pathology of AD and proteomic changes.

2018-01-25 | PXD006214 | Pride

Analysis of gene expression changes in KPT330-treated HMLE cells transduced to stably overexpress SNAI1

Project description:HMLE-SNAIL cell cultures were treated with KPT330 drug (KPT, 150 nanomolar) or vehicle (DMSO) for 24 hours, in parallel quadruplicates. KPT-330 is an Exportin 1 (XPO1) inhibitor with possible pluripotent or unexpected effects on cell signaling. Total RNA was isolated and analyzed in an Agilent two-color experiment, where four biological replicates of each condition were directly compared, expression ratios are KPT-treated condition relative to control (DMSO vehicle-treated) The experiment object was to identify genes that displayed significantly altered expression in response to KPT treatment inorder to confirm on-target drug impact and elucidate other potential effects in this cell line model.

2015-08-31 | E-GEOD-69326 | biostudies-arrayexpress

Global gene profiling of (-)-Epigallocatechin-3-gallate (EGCG)-induced neuronal death

Project description:Alzheimer’s disease (AD) is the most common form of adult-onset dementia with severe intellectual deterioration and is characterised by the accumulation of the amyloid-β (Aβ) peptides and the presence of hyperphosphorylated microtubule- associated protein, tau. (-)-Epigallocatechin-3-gallate (EGCG) – a polyphenolic catechin found in green tea leaves, not only acts as a proteasome inhibitor, it is also involved in neuroprotection. A total of 7 RNA samples were analyzed. Cultured murine primary cortical neurons were treated with 1uM EGCG for 24h (n=3) in addition to the vehicle control (n=4).

2013-12-31 | E-GEOD-22996 | biostudies-arrayexpress

RNAseq of cortex of 6-month old APPPS1 and APPPS1;Apoe-/- mice

Project description:One of the hallmarks of Alzheimer’s disease is the presence of extracellular diffuse and fibrillar plaques predominantly consisting of the amyloid-β (Aβ) peptide. ApoE influences the deposition of amyloid pathology through affecting the clearance and aggregation of monomeric Aβ in the brain. In addition to influencing Aβ metabolism, increasing evidence suggests that apoE influences microglial function in neurodegenerative diseases. Here, we characterize the impact that apoE has on amyloid pathology and the innate immune response in APPPS1∆E9 and APPPS1-21 transgenic mice. We report that Apoe deficiency reduced fibrillar plaque deposition consistent with previous studies. However, fibrillar plaques in Apoe-deficient mice exhibited a striking reduction in plaque compaction. Hyperspectral fluorescent imaging using luminescent conjugated oligothiophenes identified distinct Aβ morphotypes in Apoe-deficient mice. We also observed a significant reduction in fibrillar plaque-associated microgliosis and activated microglial gene expression in Apoe-deficient mice, along with significant increases in dystrophic neurites around fibrillar plaques. Our results suggest that apoE is critical in stimulating the innate immune response to amyloid pathology.

2018-02-15 | GSE109906 | GEO

Glycosylated clusterin species facilitate amyloid beta toxicity in human neurons.

Project description:Clusterin (CLU) is one of the most significant genetic risk factors for late onset Alzheimer’s disease. Numerous studies have now demonstrated that CLU-AD mutations and amyloid-β (Aβ) treatment alter the trafficking and localisation of glycosylated CLU. iPSCs with altered CLU trafficking were generated following the removal of CLU exon 2 by CRISPR/Cas9 gene editing. Neurons were generated from control, unedited and exon 2 -/- iPSCs and were incubated with aggregated Aβ peptides. Changes in cell death and neurite length were quantified to determine if altered CLU protein trafficking influenced neuronal sensitivity to Aβ.

2022-07-05 | GSE207466 | GEO

A Human Model of Cerebral Amyloid Angiopathy Using Neural Crest-Derived Vascular Smooth Muscle Cells

Project description:There is a growing recognition of cerebrovascular contribution to neurodegenerative diseases. Cerebral amyloid angiopathy (CAA), characterised by amyloid-beta (Aβ) deposits in the walls of intracerebral and leptomeningeal arteries, is evident in a majority of Alzheimer’s disease patients and aged people. Here, we leverage on human pluripotent stem cells to generate vascular smooth muscle cells (SMCs) from neural crest progenitors, recapitulating brain vasculature-specific attributes in Aβ metabolism. We confirm that the lipoprotein receptor, LRP1, functions in our neural crest-derived SMCs to mediate Aβ uptake and intracellular proteasomal degradation. Hypoxia significantly compromises the ability of SMCs in Aβ clearance by suppressing LRP1 expression. This enables us to develop an assay of Aβ uptake using the neural crest-derived SMCs with hypoxia as a stress paradigm. We then tested several vascular protective compounds in a high throughput format, demonstrating the value of stem cell-based phenotypic screening for novel CAA therapeutics and drug repurposing.

2015-01-21 | GSE55173 | GEO

Spermidine reduces neuroinflammation and soluble amyloid beta in an Alzheimer’s disease mouse model

Project description:Deposition of amyloid beta (Aβ) and hyperphosphorylated tau along with glial cell-mediated neuroinflammation are prominent pathogenic hallmarks of Alzheimer’s disease (AD). In recent years, impairment of autophagy has been found to be another important feature contributing to AD progression. Therefore, the potential of the autophagy activator spermidine, a small body-endogenous polyamine often used as dietary supplement, was assessed on Aβ pathology and glial cell-mediated neuroinflammation. Oral treatment of the amyloid prone AD-like APPPS1 mice with spermidine reduced neurotoxic soluble Aβ and decreased AD-associated neuroinflammation. A subsequent proteome analysis of isolated microglia confirmed the anti-inflammatory and revealed cytoskeletal effects of spermidine in APPPS1 mice. Our data highlight that the autophagy activator spermidine holds the potential to enhance Aβ degradation and to counteract microglia-mediated neuroinflammation in AD pathology.

2022-07-04 | PXD034638 | Pride

Spermidine reduces neuroinflammation and soluble amyloid beta in an Alzheimer’s disease mouse model

Project description:Deposition of amyloid beta (Aβ) and hyperphosphorylated tau along with glial cell-mediated neuroinflammation are prominent pathogenic hallmarks of Alzheimer’s disease (AD). In recent years, impairment of autophagy has been found to be another important feature contributing to AD progression. Therefore, the potential of the autophagy activator spermidine, a small body-endogenous polyamine often used as dietary supplement, was assessed on Aβ pathology and glial cell-mediated neuroinflammation. Oral treatment of the amyloid prone AD-like APPPS1 mice with spermidine reduced neurotoxic soluble Aβ and decreased AD-associated neuroinflammation during disease progression. Mechanistically, single nuclei sequencing revealed AD-associated microglia to be the main target of spermidine. This microglia population was characterized by increased AXL levels and expression of genes implicated in cell migration and phagocytosis. Our data highlight that the autophagy activator spermidine holds the potential to enhance Aβ degradation and to counteract glia-mediated neuroinflammation in AD pathology.

2022-07-04 | GSE206202 | GEO

Reduced binding of apoE4 to complement factor H promotes amyloid-β oligomerization and neuroinflammation

Project description:Alzheimer’s disease (AD) is characterized by neuroinflammation, accumulation of amyloid-β (Aβ) plaques and neuronal degeneration in the brain. The APOE4 variant of apolipoprotein E (apoE) is the most prevalent genetic risk allele associated with late-onset AD. ApoE interacts with complement regulator factor H (FH) but the role of this interaction in AD pathogenesis is unknown.

2023-05-03 | GSE193513 | GEO

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data