Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

TNFα-NF-κB activation through pathological α-Synuclein disrupts the BBB and exacerbates axonopathy

ABSTRACT: TNFα-NF-κB activation through pathological α-Synuclein disrupts the BBB and exacerbates axonopathy

PROVIDER: PRJNA1271006 | ENA |

REPOSITORIES: ENA

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
	SRR33795749_1.fastq.gz	Fastqsanger.gz
	SRR33795749_2.fastq.gz	Fastqsanger.gz
	SRR33795750_1.fastq.gz	Fastqsanger.gz
	SRR33795750_2.fastq.gz	Fastqsanger.gz
	SRR33795751_1.fastq.gz	Fastqsanger.gz

Items per page:

1 - 5 of 72

Similar Datasets

TNFα-NF-κB activation through pathological α-Synuclein disrupts the BBB and exacerbates axonopathy

Project description:Dysfunction of the blood brain barrier (BBB) is recognized as a key factor in the progression of neurodegenerative diseases, but the detailed mechanisms behind its pathogenesis and impact on neurodegeneration remain elusive. This study aimed to reveal the pathological effects of α-Synuclein (α-Syn), an aggregation protein in Synucleinopathy, on BBB integrity and function, and identify therapeutic targets for α-Syn-related vasculopathy. Using a brain endothelial cell model, we investigated the pathological effect of preformed fibril α-Syn (PFF) on BBB integrity, employing generative adversarial network (GAN) deep learning to analyze pathological changes. We found that PFF activates immune responses, increasing endothelial monolayer permeability via the TNFα-NF-κB pathway. Further in vivo studies with PFF induced α-Synucleinopathy and transgenic animal model (G2-3) revealed that α-Syn aggregation, disrupts the BBB, leading to axonal degeneration that was mitigated by treatment with a non-BBB-penetrating TNFα inhibitor, Etanercept. These findings suggest that targeting brain endothelial TNFα signaling could be a potential therapeutic approach for Synucleinopathy-related NDs.

2025-06-07 | GSE298722 | GEO

Brain endothelial GSDMD activation mediates inflammatory BBB breakdown

Project description:The blood-brain barrier (BBB) protects the central nervous system (CNS) from external assaults by pathogenic or harmful substances. BBB impairment frequently occurs during infection, inflammatory, or other pathological conditions, which causes or exacerbates a wide range of CNS diseases. Using single cell transcriptomics, we show in this study that during systemic LPS challenges, brain endothelial cells undergo Gsdmd-mediated pyroptosis and impair the integrity of the BBB, leading to profound changes in the transcriptomic landscape of brain parenchymal populations. Analyses of the scRNA-seq dataset reveal that brain endothelial cells responded strongly to systemic LPS challenge. Further analyses of the transcriptional signatures revealed that the brain parenchymal populations displayed heterogeneous responses to BBB leakage accompanied by systemic inflammation.

2024-02-22 | GSE211099 | GEO

Zebrafish BBB transcriptome

Project description:Zebrafish BBB transcriptome

| PRJNA436028 | ENA

TNFα and α-synuclein fibrils differently regulate human astrocyte immune reactivity and impair mitochondrial respiration

Project description:TNFα and α-synuclein fibrils differently regulate human astrocyte immune reactivity and impair mitochondrial respiration

| PRJNA701924 | ENA

Gene expression data of BBB and BCB two-cell embryos

Project description:We constructed one-cell stage embryos by maternal pronuclear (mPN) transfer having B6 ooplasm, B6 paternal PN (pPN), and either B6 or C3H mPN (BBB and BCB, respectively). We collected embryos of each type that were either treated (BBB+a, BCB+a) or untreated with Î±-amanitin (BBB, BCB) at the two-cell stage for microarray analysis. Comparison of the transcriptomes of these different kinds of embryos revealed genes for which expression differs according to maternal PN strain of origin, and the Î±-amanitin data revealed which of these differences is due to gene transcription, as opposed to any transcription-independent differences attributable to ooplasm-derived maternal mRNA pools. There are 4 replicates for each kind/treatment two-cell embryos (BBB, BCB, BBB+a, BCB+a).

2010-03-22 | E-GEOD-17886 | biostudies-arrayexpress

Cellular Interplay and Cytokine Hierarchy Cause Pathological Cardiac Hypertrophy in RAF1-Mutant Noonan Syndrome

Project description:Noonan syndrome (NS) is caused by mutations in RAS/ERK pathway genes, and is characterized by craniofacial, growth, cognitive and cardiac defects. NS patients with kinase-activating RAF1 alleles typically develop pathological left ventricular hypertrophy (LVH), which is reproduced in Raf1 L613V/+ knock-in mice. Here, using inducible Raf1 L613V expression, we show that LVH results from the interplay of cardiac cell types. Cardiomyocyte Raf1 L613V enhances Ca 2+ sensitivity and cardiac contractility without causing hypertrophy. Raf1 L613V expression in cardiomyocytes or activated fibroblasts exacerbates pressure overload-evoked fibrosis. Endothelial/endocardial (EC) Raf1 L613V causes cardiac hypertrophy without affecting contractility. Co-culture and neutralizing antibody experiments reveal a cytokine hierarchy (TNFα->IL6) from Raf1 L613V -expressing ECs that drives cardiomyocyte hypertrophy in vitro. Furthermore, post-natal TNFα inhibition normalizes the increased wall thickness and cardiomyocyte hypertrophy in vivo. We conclude that NS cardiomyopathy involves cardiomyocytes, ECs, and fibroblasts, TNFα/IL6 signaling components represent potential therapeutic targets, and abnormal EC signaling might contribute to other forms of LVH.

2017-05-22 | GSE95739 | GEO

Drug intervention of radiation exposure induced BBB injury via mitochondria-mediated non-infectious inflammation

Project description:Radiation-induced brain injury (RIBI) is a series of brain injuries caused by exposure to high doses of ionizing radiation, characterized by severe cognitive dysfunctions and brain necrosis.In this study, we described a biomimetic human blood-brain barrier (BBB) model that allowed to probe the responses to radiation exposure.This RNA-seq data illustrated that representative RIBI-associated pathological responses including BBB compromise, DNA break, inhibited cell proliferation, cell swelling and release of pro-inflammatory cytokines following acute radiation exposure. Based on the pathogenic mechanism study, we carried out drug screening and identified two drugs effectively ameliorated radiation-induced inflammation and BBB injury on the BBB model. Collectively, the study uncovered an unknown mitochondria-mediated inflammation involved in the pathogenesis of RIBI, indicating mitochondria can be utilized as a potential target for developing new radioprotective measures.

2025-09-03 | GSE280304 | GEO

Control, TNFα and TNFα+JNK I treated GSCs

Project description:Control, TNFα and TNFα+JNK I treated GSCs

| PRJNA799754 | ENA

Transcriptome analysis after BBB-EC migration

Project description:A monolayer of hCMEC/D3 (BBB-EC) was grown in an insert. After reaching confluency, BBB-EC were treated with TNFa and IFNg for 24h. Next, BBB-EC were washed. Tregs were isolated from human blood (both healthy donors (HD)and untreated RRMS patients) and added to the upper chamber of the insert or were cultured in the BBB-EC medium as control (untouched_1). They were let to migrate for 24h and the upper fraction (non-migrated_2) and lower fraction (migrated_3) were collected.

2024-02-11 | GSE255171 | GEO

Radiation exposure induced BBB injury via mitochondria-mediated non-infectious inflammation

Project description:Radiation-induced brain injury (RIBI) is a series of brain injuries caused by exposure to high doses of ionizing radiation, characterized by severe cognitive dysfunctions and brain necrosis.In this study, we described a biomimetic human blood-brain barrier (BBB) model that allowed to probe the responses to radiation exposure.This RNA-seq data illustrated that representative RIBI-associated pathological responses including BBB compromise, DNA break, inhibited cell proliferation, cell swelling and release of pro-inflammatory cytokines following acute radiation exposure. Collectively, the study uncovered an unknown mitochondria-mediated inflammation involved in the pathogenesis of RIBI, indicating mitochondria can be utilized as a potential target for developing new radioprotective measures.

2025-09-03 | GSE280303 | GEO

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

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