Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Increased expression of myelin-associated genes in frontal cortex of SNCA overexpressing rats and Parkinson’s disease patients

ABSTRACT: Increased expression of myelin-associated genes in frontal cortex of SNCA overexpressing rats and Parkinson’s disease patients

PROVIDER: PRJNA633095 | ENA |

REPOSITORIES: ENA

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
	SRR11795763_1.fastq.gz	Fastqsanger.gz
	SRR11795763_2.fastq.gz	Fastqsanger.gz
	SRR11795764_1.fastq.gz	Fastqsanger.gz
	SRR11795764_2.fastq.gz	Fastqsanger.gz
	SRR11795765_1.fastq.gz	Fastqsanger.gz

Items per page:

1 - 5 of 40

Similar Datasets

Increased expression of myelin-associated genes in frontal cortex of SNCA overexpressing rats and Parkinson’s disease patients

Project description:Parkinson’s disease is an age-dependent neurodegenerative disorder. Besides characteristic motor symptoms, patients suffer from cognitive impairments linked to pathology in cortical areas. Due to obvious challenges in tracing molecular perturbations underlying alterations in human brain over time, we took advantage of a well-characterized rat model. Using RNA sequencing, we profiled the frontocortical transcriptome of post-mortem patient samples and aligned expression changes with perturbation patterns obtained in the model at 5 and 12 months of age reflecting a presymptomatic and symptomatic time point. Integrating cell type-specific reference data, we identified a shared expression signature between both species that pointed to oligodendrocyte-specific, myelin-associated genes. Drawing on longitudinal information from the model, their nearly identical upregulation in both species allowed tracing them to two distinctive perturbance modes they originate from. While one mode exhibited age-independent alterations that affected genes like PLP1, the other mode, impacting on genes like MAG, was characterized by interferences of disease gene and adequate adaptations of gene activity along ageing. Our results highlight that even for a small set of functionally linked genes distinct interference mechanisms may underly disease progression that cannot be distinguished by examining the terminal point alone but instead require longitudinal interrogation of the system.

2020-12-21 | GSE150646 | GEO

Proteomic investigation of whole cortex and synaptosomes from rats with a familial Parkinson’s G51D mutation in the Snca gene.

Project description:The glycine-51 (G51) codon in exon 3 of the rat Snca gene, encoding alpha-synuclein, was mutated to aspartic acid using CRISPR/Cas9 to generate the SncaG51D rat model of Parkinson’s (Morley et al. 2023). The G51D mutation causes an aggressive form of Parkinson’s and dementia with Lewy bodies in humans. The brains from four 6-month old rats of wild-type, heterozygous, and homozygous genotypes (Snca+/+, SncaG51D/+ and SncaG51D/G51D) were harvested and all 12 brains were bisected down the midline. Frontal cortex was isolated from one half, and synaptosomes were prepared from the other half. Following quality control the samples were processed for TMT-mass spectrometry by the Fingerprints Facility, University of Dundee. MaxQuant Version 1.6.0.16 was used for the assignment of peptides to protein using the uniport-rat-jan2018.fasta file. Pairwise comparisons were made between the different mutant samples and Snca+/+ for both the cortical and synaptosome samples. Morley V, Dolt KS, Alcaide-Corral CJ, Walton T, Lucatelli C, Mashimo T, Tavares AAS & Kunath T (2023) In vivo18F-DOPA PET imaging identifies a dopaminergic deficit in a rat model with a G51D α-synuclein mutation. Front. Neurosci. 17, 1095761.

2024-09-04 | PXD044776 | Pride

Increased expression of myelin-associated genes in frontal cortex of <i>SNCA</i> overexpressing rats and Parkinson's disease patients.

Project description:Parkinson's disease (PD) is an age-dependent neurodegenerative disorder. Besides characteristic motor symptoms, patients suffer from cognitive impairments linked to pathology in cortical areas. Due to obvious challenges in tracing the underlying molecular perturbations in human brain over time, we took advantage of a well-characterized PD rat model. Using RNA sequencing, we profiled the frontocortical transcriptome of post-mortem patient samples and aligned expression changes with perturbation patterns obtained in the model at 5 and 12 months of age reflecting a presymptomatic and symptomatic time point. Integrating cell type-specific reference data, we identified a shared expression signature between both species that pointed to oligodendrocyte-specific, myelin-associated genes. Drawing on longitudinal information from the model, their nearly identical upregulation in both species could be traced to two distinctive perturbance modes. While one mode exhibited age-independent alterations that affected genes including proteolipid protein 1 (PLP1), the other mode, impacting on genes like myelin-associated glycoprotein (MAG), was characterized by interferences of disease gene and adequate expression adaptations along aging. Our results highlight that even for a group of functionally linked genes distinct interference mechanisms may underlie disease progression that cannot be distinguished by examining the terminal point alone but instead require longitudinal interrogation of the system.

| S-EPMC7732335 | biostudies-literature

a-Synuclein Antisense Transcript SNCA-AS1 regulates synapses- and aging-related genes suggesting its implication in Parkinson’s Disease

Project description:SNCA protein product, a-synuclein, is widely renowned for its role in synaptogenesis and implication in both aging and Parkinson’s Disease (PD), but research efforts are still needed to elucidate its physiological functions and mechanisms of regulation. In this work, we aim to characterize SNCA-AS1, antisense transcript to the SNCA gene, and its implications in cellular processes. The overexpression of SNCA-AS1 upregulates both SNCA and a-synuclein, and through RNA-seq analysis we investigated the transcriptomic changes of which both genes are responsible. We highlight how they impact neurites extension and synapses’ biology, through specific molecular signatures. We report a reduced expression of markers associated with synaptic plasticity, and we specifically focus on GABAergic and dopaminergic synapses, for their relevance in aging processes and PD, respectively. A reduction in SNCA-AS1 expression leads to the opposite effect. As part of this signature is co-regulated by the two genes, we discriminate between functions elicited by genes specifically altered by SNCA-AS1 or SNCA’s overexpression, observing a relevant role for SNCA-AS1 in synaptogenesis through a shared molecular signature with SNCA. We also highlight how numerous deregulated pathways are implicated in aging-related processes, suggesting that SNCA-AS1 could be a key player in cellular senescence, with implications for aging-related diseases. Indeed, the upregulation of SNCA-AS1 leads to alterations in numerous PD specific genes, with an impact highly comparable to that of SNCA’s upregulation. Our results show that SNCA-AS1 elicits its cellular functions through the regulation of SNCA, with a specific modulation of synaptogenesis and senescence, presenting implications in PD.

2021-12-23 | GSE186255 | GEO

Transcription regulation of SNCA by dystonia type 6 gene product THAP1 [4C-Seq]

Project description:The predominantly function of THAP1 has been defined as a transcription factor, but how it regulates gene expression in human neurons is not well understood. Here, we found that THAP1 is able to regulate the expression of alpha-synuclein (SNCA), a key protein in Parkinson’s disease (PD).

2022-09-28 | GSE141277 | GEO

Transcription regulation of SNCA by dystonia type 6 gene product THAP1 [ChIP-seq]

2022-09-28 | GSE141244 | GEO

Transcription regulation of SNCA by dystonia type 6 gene product THAP1 [Rat_ChIP-seq]

2022-09-28 | GSE201686 | GEO

Transcription regulation of SNCA by dystonia type 6 gene product THAP1 [RNA-Seq]

2022-09-28 | GSE147633 | GEO

Enriched environmental conditions modify the gut microbiome composition and fecal markers of inflammation in Parkinson’s disease

Project description:We used a transgenic mouse model overexpressing the complete human SNCA genes modeling familial and sporadic forms of Parkinson’s disease to study whether environmental conditions such as standard versus enriched environment changes the gut microbiome and influences disease progression.

2019-10-01 | GSE137213 | GEO

Vimentin network dysregulation mediates neurite deficits in SNCA duplication Parkinson’s patient-derived midbrain neurons

Project description:Duplication of the SNCA gene (SNCADupl), linked to elevated levels of alpha-synuclein (aSyn), is a genetic cause of Parkinson's disease (PD). Our prior work with human-induced pluripotent stem cell (hiPSC)-derived midbrain neurons generated from PD SNCADupl patients identified neuritic deficits, accompanied by decreased levels of cytoskeletal element b-tubulin-III (bTubIII). To explore mechanisms underlying these effects in SNCADupl neurons, we employed CRISPR/Cas9 to generate isogenic control hiPSCs. Isogenic correction of SNCA dosage restored SNCADupl-induced neurite defects and bTubIII levels. Multi-omics analyses revealed SNCADupl-induced alterations in neuronal differentiation, with a notable downregulation of PAX6. Moreover, SNCADupl induced an upregulation of vimentin. Further characterization revealed heightened vimentin truncation, associated with altered distribution and organization. Similar changes in vimentin levels and truncation were observed in post-mortem putamen tissue from sporadic PD patients. Notably, targeting vimentin with okadaic acid and withaferin A restored bTubIII- and neurite-associated defects, suggesting its potential to prevent aSyn-mediated neuritic degeneration.

2025-07-16 | PXD063433 | Pride

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