Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Studying the selectivity of a small molecule Synucleozid on transcriptome

ABSTRACT: One strategy to drugging undruggable proteins is to directly target the mRNA that encodes them, thereby inhibit translation and reducing protein levels. Inforna, a sequence-based design approach to target RNA, enables the design of a small molecule Synucleozid that binds SNCA mRNA which encodes alpha-synuclein. Herein, we investigate the selectivity of Synucleozid on the whole transcriptome. Based on mechanistic studies, Synucleozid targets IRE locates in 5' UTR of SNCA mRNA and reduces alpha-synuclein protein levels by decreasing the amount of SNCA mRNA loaded into polysomes. Different from alpha-synuclein siRNA, Synucleozid binds mRNA and affect its function without regulating mRNA expression.

ORGANISM(S): Homo sapiens

PROVIDER: GSE129590 | GEO | 2019/12/11

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

Single cell RNA sequencing analysis of midbrain organoids with SNCA gene triplication modeling key features of synuclienopathy

Project description:SNCA, the first gene associated with Parkinson’s disease, encodes the α-synuclein protein, the predominant component within pathological inclusions termed Lewy bodies. We use 3D midbrain organoids, differentiated from human induced pluripotent stem cells derived from patients carrying a triplication of the SNCA gene and from CRISPR/Cas9 corrected isogenic control iPSCs. These human midbrain organoids recapitulate key features of α-synuclein pathology observed in the brains of patients with synucleinopathies. We used single cell RNA sequencing to characterize the cell types within these organoids. We find an equal proportion of neuronal and glial cells. The neuronal populations consist of dopmainergic, excitatory and inhibitory neurons in early and late stages of maturation as well as neural precursor cells. The glial populations consist of dividing radial glia, radial glia, astrocytes and early oligodendorcytes.

2021-11-02 | GSE186780 | GEO

Expression data from Parkison's iPSCs with four copies of SNCA, and equivalent cell lines from an unaffected first degree relative

Project description:A major barrier to research on Parkinson’s disease (PD) is inaccessibility of diseased tissue for study. One solution is to derive induced pluripotent stem cells (iPSCs) from patients with PD and differentiate them into neurons affected by disease. We created an iPSC model of PD caused by triplication of SNCA encoding α-synuclein. α-Synuclein dysfunction is common to all forms of PD, and SNCA triplication leads to fully penetrant familial PD with accelerated pathogenesis. After differentiation of iPSCs into neurons enriched for midbrain dopaminergic subtypes, those from the patient contain double α-synuclein protein compared to those from an unaffected relative, precisely recapitulating the cause of PD in these individuals. A measurable biomarker makes this model ideal for drug screening for compounds that reduce levels of α-synuclein, and for mechanistic experiments to study PD pathogenesis. This gene expression microarray study was carried out as part of the validation process for demonstrating that the generated iPSC lines are pluripotent. 5 samples were analysed: two clonal iPSC lines from each of two genotypes (four in total; AST denoting alpha-synuclein triplication and NAS denoting normal alpha-synuclein), a human embryonic stem cell line (SHEF4). All cultured in self-renewal conditions, mTeSR1

2011-09-14 | E-GEOD-30792 | biostudies-arrayexpress

SNP data from genomic DNA from a subject, fibroblasts, iPSCs and neurons with four copies of SNCA, and genomic DNA from an unaffected first degree relative and equivalent cell lines

Project description:A major barrier to research on Parkinson’s disease (PD) is inaccessibility of diseased tissue for study. One solution is to derive induced pluripotent stem cells (iPSCs) from patients with PD and differentiate them into neurons affected by disease. We created an iPSC model of PD caused by triplication of SNCA encoding α-synuclein. α-Synuclein dysfunction is common to all forms of PD, and SNCA triplication leads to fully penetrant familial PD with accelerated pathogenesis. After differentiation of iPSCs into neurons enriched for midbrain dopaminergic subtypes, those from the patient contain double α-synuclein protein compared to those from an unaffected relative, precisely recapitulating the cause of PD in these individuals. A measurable biomarker makes this model ideal for drug screening for compounds that reduce levels of α-synuclein, and for mechanistic experiments to study PD pathogenesis. This SNP microarray study was carried out to confirm presence of SNCA triplication in the affected subject and the derived cell lines.

2011-09-15 | GSE28366 | GEO

SNP data from genomic DNA from a subject, fibroblasts, iPSCs and neurons with four copies of SNCA, and genomic DNA from an unaffected first degree relative and equivalent cell lines

Project description:A major barrier to research on Parkinson’s disease (PD) is inaccessibility of diseased tissue for study. One solution is to derive induced pluripotent stem cells (iPSCs) from patients with PD and differentiate them into neurons affected by disease. We created an iPSC model of PD caused by triplication of SNCA encoding ?-synuclein. ?-Synuclein dysfunction is common to all forms of PD, and SNCA triplication leads to fully penetrant familial PD with accelerated pathogenesis. After differentiation of iPSCs into neurons enriched for midbrain dopaminergic subtypes, those from the patient contain double ?-synuclein protein compared to those from an unaffected relative, precisely recapitulating the cause of PD in these individuals. A measurable biomarker makes this model ideal for drug screening for compounds that reduce levels of ?-synuclein, and for mechanistic experiments to study PD pathogenesis. This SNP microarray study was carried out to confirm presence of SNCA triplication in the affected subject and the derived cell lines. 11 samples were analysed: genomic DNA from the two subjects in the study, the two parent fibroblast lines (AST denoting alpha-synuclein triplication and NAS denoting normal alpha-synuclein), two iPSC lines from each parent fibroblast line (four in total), a human embryonic stem cell line (SHEF4) and two neuronal samples one each from AST and NAS iPSCs).

2011-09-14 | E-GEOD-28366 | biostudies-arrayexpress

Expression data from fibroblasts, iPSCs and neurons with four copies of SNCA, and equivalent cell lines from an unaffected first degree relative

Project description:A major barrier to research on Parkinson’s disease (PD) is inaccessibility of diseased tissue for study. One solution is to derive induced pluripotent stem cells (iPSCs) from patients with PD and differentiate them into neurons affected by disease. We created an iPSC model of PD caused by triplication of SNCA encoding α-synuclein. α-Synuclein dysfunction is common to all forms of PD, and SNCA triplication leads to fully penetrant familial PD with accelerated pathogenesis. After differentiation of iPSCs into neurons enriched for midbrain dopaminergic subtypes, those from the patient contain double α-synuclein protein compared to those from an unaffected relative, precisely recapitulating the cause of PD in these individuals. A measurable biomarker makes this model ideal for drug screening for compounds that reduce levels of α-synuclein, and for mechanistic experiments to study PD pathogenesis. This gene expression microarray study was carried out as part of the validation process for demonstrating that the generated iPSC lines are pluripotent. 15 samples were analysed: the two parent fibroblast lines (AST denoting alpha-synuclein triplication and NAS denoting normal alpha-synuclein), two iPSC lines from each parent fibroblast line (four in total), a human embryonic stem cell line (SHEF4) and eight neuronal samples (each iPSC line differentiated into a neuronal population enriched for dopaminergic neurons, at two different time points).

2011-09-14 | E-GEOD-28365 | biostudies-arrayexpress

Patterns of cancer development and progression in the protein-protein interaction network

2012-07-01 | GSE31180 | GEO

Patterns of cancer development and progression in the protein-protein interaction network

Project description:For this study we selected a gene, α-synuclein (SNCA), that is consistently under-expressed in MCF7 cells and breast tumors. Following transfection with an SNCA expression construct, two stable MCF7 clones (named MCF7-SNCA #1 and 2) were selected and examined for expression differences relative to the parental MCF7 cells. MCF7 cells were transfected with an expression vector containing the full-length SNCA sequence. After selection with blasticidin, two different clones were isolated and examined for expression differences relative to the parental MCF7 cells.

2012-06-30 | E-GEOD-31180 | biostudies-arrayexpress

Expression data from Parkinson's iPSCs with four copies of SNCA, and equivalent cell lines from an unaffected first degree relative

2011-09-15 | GSE30792 | GEO

Expression data from fibroblasts, iPSCs and neurons with four copies of SNCA, and equivalent cell lines from an unaffected first degree relative

2011-09-15 | GSE28365 | GEO

Molecular-genetic correlates of fatigue in cancer patients receiving localized external beam radiation therapy

Project description:The etiology behind cancer-related fatigue (CRF) is currently unknown. The physiological mechanisms of CRF are based on limited evidence that genetic factors, energy expenditure, metabolism, aerobic capacity, and the individual's immune response to inflammation are responsible for the experience of CRF. Gene expression profiling using microarray analysis from white blood cells of men with non-metastatic prostate cancer shows significant, differential expression of 463 probesets during localized external beam radiation therapy (EBRT). Pathway analysis shows a central role of SNCA (alpha-synuclein gene) among these differentially expressed probesets. Significant expression of SNCA was confirmed by qPCR (p<.001) and ELISA (p<.001) over time during EBRT. A significant correlation was noted between averaged fatigue scores and delta CT values of SNCA expression using confirmatory qPCR over time during EBRT (R=-.90, p=.006). Development of fatigue experienced by these men during EBRT may be mediated by SNCA expression. Pathways related to alpha-synuclein may serve as useful biomarkers to understand the mechanisms behind the development of fatigue. A longitudinal design exploring the association between changes in gene expression and fatigue symptoms of men with non-metastatic prostate cancer receiving external beam radiation therapy. Blood samples were collected from ten subjects at 7 timepoints for microarray analysis: baseline (before EBRT); days 1, 7, 14, 21, 42 of EBRT; and 30 days post-EBRT. Baseline data obtained from subjects were compared to data obtained from age-, race-, and gender-matched healthy controls.

2012-12-21 | E-GEOD-30174 | biostudies-arrayexpress

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