Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Neural cell state modulation by PARK2 and dopaminergic neuroprotection by small molecule Parkin agonism [scRNA-seq]

ABSTRACT: Parkin, an E3 ubiquitin ligase encoded by PARK2, plays a key role in both hereditary and sporadic Parkinson’s disease (PD), yet there are no therapies currently available that can target this important pathway. Here, we show that Parkin is critical for successful neuronal differentiation and survival, and we develop small-molecule Parkin agonists that can protect dopaminergic neurons. Upon differentiation of neural progenitor cells, loss of Parkin results in a reduced capacity to maintain neuronal cell state, dopaminergic neuronal phenotypes, and stress resistance. Moreover, Parkin loss disrupted cell morphology and the stability of neurites. Transcriptional and single-cell analyses reveal that Parkin controls critical pathways regulating stem-like cell transitions and is needed for stable neuronal maturation. We also examined the effects of FB231, a small molecule enhancer of Parkin E3 ligase activity, in models of PD. FB231 reduced pathological α-synuclein and enhanced cell survival in human iPSC-derived dopaminergic neurons treated with α-synuclein preformed fibrils. Furthermore, FB231 attenuated α-synuclein pathology and dopaminergic neurodegeneration in a gut α-synuclein murine model of PD. Our findings support that Parkin plays a crucial role in maintaining neuronal homeostasis and that pharmacologic activation of Parkin may be a promising strategy to attenuate neurodegeneration in PD.

ORGANISM(S): Mus musculus

PROVIDER: GSE337989 | GEO | 2026/07/13

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

Neural cell state modulation by PARK2 and dopaminergic neuroprotection by small molecule Parkin agonism [RNA-Seq]

Project description:Parkin, an E3 ubiquitin ligase encoded by PARK2, plays a key role in both hereditary and sporadic Parkinson’s disease (PD), yet there are no therapies currently available that can target this important pathway. Here, we show that Parkin is critical for successful neuronal differentiation and survival, and we develop small-molecule Parkin agonists that can protect dopaminergic neurons. Upon differentiation of neural progenitor cells, loss of Parkin results in a reduced capacity to maintain neuronal cell state, dopaminergic neuronal phenotypes, and stress resistance. Moreover, Parkin loss disrupted cell morphology and the stability of neurites. Transcriptional and single-cell analyses reveal that Parkin controls critical pathways regulating stem-like cell transitions and is needed for stable neuronal maturation. We also examined the effects of FB231, a small molecule enhancer of Parkin E3 ligase activity, in models of PD. FB231 reduced pathological α-synuclein and enhanced cell survival in human iPSC-derived dopaminergic neurons treated with α-synuclein preformed fibrils. Furthermore, FB231 attenuated α-synuclein pathology and dopaminergic neurodegeneration in a gut α-synuclein murine model of PD. Our findings support that Parkin plays a crucial role in maintaining neuronal homeostasis and that pharmacologic activation of Parkin may be a promising strategy to attenuate neurodegeneration in PD.

2026-07-13 | GSE337982 | GEO

Transcriptomic dataset of neural progenitors differentiated from Parkinson's disease patient induced pluripotent stem cells with heterozygous PARK2 junction mutations transduced with a lentivector containing PARK2 cDNA.

Project description:Parkinson's disease (PD) is a neurodegenerative pathology caused by progressive loss of dopaminergic neurons in the substantia nigra. Juvenile PD is known to be strongly associated with mutations in the PARK2 gene encoding E3 ubiquitin ligase Parkin. Despite numerous studies, molecular mechanisms that trigger PD still remain unknown. Here, we presented the transcriptome profile for neural progenitors (NP) which were obtained from iPSCs of Parkinson's disease patient, transduced with lentiviral particles carrying the full-length copy of cDNA PARK2. Transcriptome profiles were generated on an NextSeq 500 System (Illumina). A comparative transcriptome analysis of this data along with transcriptome profiles for NP of healthy donors and other patients with PD will allow determining the contribution of mutations of the PARK2 gene to PD pathogenesis and identifying genes whose expression depends on PARK2 overexpression.

2022-06-03 | GSE205235 | GEO

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

Proteomic analysis of human PARK2 knockout iPSC-derived neurons

Project description:Mitochondrial dysfunction plays a major role in the pathogenesis of sporadic Parkinson’s disease (PD) and familial PD caused by mutations in the PARK2 gene. The protein, parkin, is vital for mitochondrial function, but the lack of key PD phenotypes in PARK2 knockout (KO) rodent models has hindered investigations into parkin’s role in PD pathogenesis. Human isogenic induced pluripotent stem cell (iPSC) lines with and without PARK2 KO enable studies of the effect of parkin dysfunction in dopaminergic neuronal cultures.

2019-09-03 | PXD007871 | Pride

Targeting MLKL alleviates neuroinflammation and prevents motor neuron damage in Parkinson’s traits

Project description:Neuroinflammatory processes are a prominent contributor to the pathology of Parkinson’s disease (PD), characterized by the progressive loss of dopaminergic neurons in the substantia nigra (SN) and deposits of α-synuclein aggregates. MLKL-mediated cell necroptosis might occur in the onset of PD and lead to neuronal dopaminergic degeneration. However, the link between α-synuclein, neuroinflammatory processes, and neurodegeneration in PD remains unclear. Here, our in vitro study indicated that inhibition of MLKL exerted a protective effect against 6-OHDA- and TNF-α-induced neuronal cell death. Furthermore, we created a mouse model (Tg-Mlkl-/-) with typical progressive Parkinson traits by crossbreeding SNCA A53T transgenic mice with MLKL knockout mice. Tg-Mlkl-/ mice displayed dramatically improved motor symptoms and reduced hyperphosphorylated α-synuclein expression. More data suggested that MLKL deficiency protected dopaminergic neurons, blocked neuronal cell death, and attenuated neuroinflammation by inhibiting the activation of the microglia and astrocytes. Single-cell RNA-seq analysis revealed reduced microglial cells and damped neuron death in the SN of the Tg-Mlkl-/- mice. Subcluster analysis identified a unique cell type-specific transcriptome profiling in the MLKL deficiency mice. Thus, MLKL represents a critical therapeutic target for reducing neuroinflammation and preventing dopaminergic neuron degeneration.

2023-12-14 | GSE197679 | GEO

Proteomic characterisation of lysosomal and mitochondrial perturbations in human iPSC-derived neurons with PARK2 mutation

2019-07-26 | PXD008894 | Pride

Pingping_2025_NC_N-acetyl-l-leucine_PD

Project description:Abstract N-acetyl-L-leucine (NALL), a derivative of the branched-chain amino acid leucine, has shown therapeutic potential in neurodegenerative diseases, including in prodromal stages of Parkinson s disease (PD). However, the mechanism of its protective effects has been largely unknown. Using discovery-based proteomics, we found that treatment with NALL led to upregulation of lysosomal, mitochondrial, and synaptic proteins in PD patient-derived dopaminergic neurons. NALL reduced levels of pathological pS129-alpha-synuclein in dopaminergic neurons from patients harboring GBA1 or LRRK2 mutations. This decrease in pS129-syn was dependent on serine protease HTRA1 that was induced by NALL treatment of dopaminergic neurons. NALL also upregulated expression of wild-type parkin in both GBA1 and LRRK2 mutant neurons, leading to an increase in functional dopamine transporter and synaptic membrane-associated synaptojanin-1, suggesting improved synaptic function. Furthermore, NALL treatment of mutant LRRK2R1441C knock-in mice led to decreased pS129-alpha-synuclein, increased parkin and improved dopamine-dependent motor learning deficits. These findings highlight the therapeutic potential of NALL in PD by its protective effects on alpha-synuclein pathology and synaptic function in vulnerable dopaminergic neurons.

2025-04-10 | MSV000097594 | MassIVE

Parkinson's disease genes VPS35 and EIF4G1 interact genetically and converge on alpha-synuclein

Project description:Parkinson's disease (PD) is a common human neurodegenerative movement disorder. Studies of the genetic forms of PD have helped to reveal disease mechanisms. Functional interactions between some Parkinson's disease (PD) genes, like PINK1 and parkin, have been identified, but whether other ones interact remains elusive. Here we report an unexpected genetic interaction between two PD genes, VPS35 and EIF4G1. We provide evidence that EIF4G1 upregulation causes defects associated with protein misfolding. Expression of a sortilin protein rescues these defects, downstream of VPS35, suggesting a potential role for sortilins in PD. We also show interactions between VPS35, EIF4G1 and alpha-synuclein, a protein with a key role in the pathogenesis of both sporadic and familial PD. We extend our findings from yeast to an animal model and show these interactions are conserved in neurons. We also connect VPS35 impairments to neurodegeneration in alpha-synuclein transgenic mice. Our studies reveal unexpected genetic and functional interactions between two seemingly unrelated PD genes and functionally connect them to alpha-synuclein pathobiology in yeast, worms, and mouse. Finally, we provide a resource of candidate PD genes for future genetic and functional interrogation. Ribosome profiling (RiboSeq) of wild type and VPS35 deletion yeast strains, with or without overexpression of the TIF4631 initiation factor

2014-12-19 | E-GEOD-64304 | biostudies-arrayexpress

Marine Bacterium Stutzerimonas stutzeri Mitigates Parkinson's disease Pathology in C. elegans via Ferroptosis Modulation

Project description:Parkinson's disease (PD) is a rapidly escalating neurodegenerative disorder marked by dopaminergic neurodegeneration, α-synuclein aggregation, and motor and non-motor impairments. Current therapies largely provide symptomatic relief and fail to prevent disease progression, underscoring the need for novel disease-modifying strategies. The marine biome has emerged as an unexplored reservoir of bioactive metabolites with neuroprotective potential, yet their therapeutic relevance in PD remains incompletely explored. Here, we report that Stutzerimonas stutzeri, a marine bacterium isolated from the Gulf of Mannar, exerts robust neuroprotective effects in Caenorhabditis elegans PD models. Dietary administration of S. stutzeri rescued dopaminergic neuronal loss, mitigated α-synuclein expression, and improved motor and sensory phenotypes. Mechanistic analyses revealed suppression of ferroptosis, evidenced by restoration of iron homeostasis, attenuation of lipid peroxidation, and recovery of ftn-1 expression. Our findings establish S. stutzeri as a previously unrecognized marine-derived therapeutic prospect for PD intervention and highlight ferroptosis modulation as a tractable therapeutic axis in neurodegeneration.

2026-06-03 | GSE312231 | GEO

Expression data from PARK2 overexpression in U251 cells

Project description:PARK2 (PARKIN) is an E3 ubiquitin ligase whose dysfunction has been associated with the progression of Parkinsonism and human malignancies, and its role in cancer remains to be explored. In this study, we investigated its role in glioma. We used microarrays to detail the global programme of gene expression upon PARK2 overexpression in U251 cells U251 cells with PARK2 overexpression or control (GFP) were subjected for RNA extraction and hybridization on Affymetrix microarrays.

2014-10-03 | E-GEOD-61973 | 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