Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Insulin resistance disrupts midbrain metabolic and functional homeostasis and aggravates dopaminergic neuron loss in GBA-PD via FOXO1 overexpression [WTs]

ABSTRACT: Insulin resistance disrupts midbrain metabolic and functional homeostasis and aggravates dopaminergic neuron loss in GBA-PD via FOXO1 overexpression [WTs]

PROVIDER: PRJNA993990 | ENA |

REPOSITORIES: ENA

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
	SRR25243533.fastq.gz	Fastqsanger.gz
	SRR25243534.fastq.gz	Fastqsanger.gz
	SRR25243535.fastq.gz	Fastqsanger.gz
	SRR25243536.fastq.gz	Fastqsanger.gz
	SRR25243537.fastq.gz	Fastqsanger.gz

Items per page:

1 - 5 of 6

Similar Datasets

Insulin resistance disrupts midbrain metabolic and functional homeostasis and aggravates dopaminergic neuron loss in GBA-PD via FOXO1 overexpression [WTvsGBA]

Project description:Growing evidence indicates that Type 2 diabetes (T2D) is associated with an increased risk of developing PD Parkinson’s disease (PD) through shared disease mechanisms. Studies show that insulin resistance, which is the driving pathophysiological mechanism of T2D plays a major role in neurodegeneration by impairing neuronal functionality, metabolism, and survival. To better understand the importance of insulin signalling in the human midbrain, which is the most affected brain region in PD, we expose IPSC-derived human midbrain organoids from healthy individuals and GBA-N370S mutation-carrying PD patients to either high insulin concentrations, promoting insulin resistance, or to more physiological insulin concentrations restoring normal insulin signalling function. We are able to show that insulin resistance compromises dopaminergic neuron and dopamine levels in the midbrain organoids of healthy donors. Moreover, insulin-resistant organoids display diminished neuronal activity and reduced metabolic efficiency. Furthermore, our findings demonstrate FOXO1 role in GBA-PD phenotype severity and show the potential beneficial effects of the anti-diabetic drug Pioglitazone in GBA-PD treatment. Overall, our results highlight insulin resistance as a significant target in PD prevention and disease-modifying therapy.

2024-10-01 | GSE237115 | GEO

Insulin resistance disrupts midbrain metabolic and functional homeostasis and aggravates dopaminergic neuron loss in GBA-PD via FOXO1 overexpression [WTs]

2024-10-01 | GSE237114 | GEO

Insulin resistance disrupts midbrain metabolic and functional homeostasis and aggravates dopaminergic neuron loss in GBA-PD via FOXO1 overexpression.

Project description:Insulin resistance disrupts midbrain metabolic and functional homeostasis and aggravates dopaminergic neuron loss in GBA-PD via FOXO1 overexpression.

| PRJNA993986 | ENA

Cell cycle arrest of neural progenitors causes impaired dopaminergic neuronal differentiation in GBA associated Parkinson’s disease midbrain organoids [2]

Project description:The mechanisms underlying Parkinson's disease (PD) etiology are only partially understood despite intensive research conducted in the field. Recent evidence suggests that early neurodevelopmental defects might play a role in cellular susceptibility to neurodegeneration. To study the early developmental contribution of GBA mutations in PD we used patient-derived iPSCs carrying a heterozygous N370S mutation in the GBA gene. Patient-specific midbrain organoids displayed GBA-PD relevant phenotypes such as reduction of GCase activity, autophagy impairment and mitochondrial dysfunction. Genome-scale metabolic (GEM) modeling predicted changes in lipid metabolism which were validated with lipidomics analysis, showing significant differences in the lipidome of GBA-PD. In addition, patient-specific midbrain organoids exhibited an increase in the neural progenitor population showing signs of cellular senescence. This was accompanied by a decrease in the number and complexity of dopaminergic neurons. These results provide insights into how GBA mutations may lead to neurodevelopmental defects thereby predisposing to PD pathology.

2022-07-24 | GSE208783 | GEO

Cell cycle arrest of neural progenitors causes impaired dopaminergic neuronal differentiation in GBA associated Parkinson’s disease midbrain organoids [1]

2022-07-24 | GSE208781 | GEO

Insulin resistance disrupts midbrain metabolic and functional homeostasis and aggravates dopaminergic neuron loss in GBA-PD via FOXO1 overexpression [WTvsGBA]

Project description:Insulin resistance disrupts midbrain metabolic and functional homeostasis and aggravates dopaminergic neuron loss in GBA-PD via FOXO1 overexpression [WTvsGBA]

| PRJNA993989 | ENA

Parkinson’s disease blood biomarkers correspond to a selectively vulnerable group of dopaminergic neurons

Project description:Blood mRNA biomarker validation of the Luxembourgish PD cohort by single cell RNAseq in GBA-PD midbrain organoids identifies a PD vulnerable dopaminergic neuron subcluster, with transcriptionally overactive mitochondria that is lost upon PD. Deep phenotyping of patient derived GBA-N409S midbrain organoids confirms the altered mitochondrial activity, increased ROS and TH+ dopaminergic neuronal cell loss in PD. To identify molecular targets underlying the increased dopaminergic vulnerability in GBA-N409S midbrain organoids blood cohort mRNA and miRNA biomarkers were integrated, revealing ALDH1A1, an aldehyde dehydrogenase involved in dopamine metabolism and reactive aldehyde clearance as potential candidate gene. Moreover, cohort metabolite biomarker validation revealed retinoic acid metabolism as potential pathway involved in ALDH1A1 dependent dopaminergic susceptibility. Whereas toxin induced ALDH1A1 reduction alone was not sufficient to induce dopaminergic neuron cell death in healthy organoids retinoic acid treatment rescued GBA-N409S dopaminergic neuron loss in GBA-N409S PD.

2025-01-01 | GSE278769 | GEO

RNA-SEQ profiling of mouse whole midbrain and dopaminergic neurons from the mouse mid-brain

Project description:RNA-SEQ profiling of mouse whole midbrain and dopaminergic neurons from the mouse mid-brain Murine whole midbrain and murine midbrain dopaminergic neurons

2015-07-27 | E-GEOD-64526 | biostudies-arrayexpress

ChIP-seq analysis of Foxa2 binding sites in midbrain dopaminergic progenitors

Project description:Embryonic stem (ES) cells were differentiated in culture to midbrain dopaminergic (mDA) progenitors and subjected to ChIP-seq analysis to resolve genome-wide binding sites of forkhead box protein A2 (Foxa2). Foxa2 was found to directly regulate multiple lineage pathways to specify midbrain dopaminergic and floor plate progenitor identity.

2012-07-01 | E-MTAB-1137 | biostudies-arrayexpress

Cell cycle arrest of neural progenitors causes impaired dopaminergic neuronal differentiation in GBA associated Parkinson’s disease midbrain organoids

Project description:Cell cycle arrest of neural progenitors causes impaired dopaminergic neuronal differentiation in GBA associated Parkinson’s disease midbrain organoids

| PRJNA860990 | ENA

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