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Ropinirole improves the amyotrophic lateral sclerosis phenotype of TDP43-mutant iPSC-derived motor neurons via a D2R-independent mechanism

GSE283507 Homo sapiens (human) RNA-seq (gene expression) 54 samples Submitted 2025/08/27 Platform GPL24676
At a glance

RNA-seq (gene expression) · human · 54 samples

What it is
RNA-seq (gene expression)Gene activity measured by sequencing. The summary does not mention single-cell work, so this is most likely bulk: one average per sample, the usual starting point for comparing groups.
Organism
Homo sapiens (human)
Samples
54 samples: 18 conditions, mostly in triplicateGroups are read from the sample names, not from the paper. Check the list below.
Data you can get
A processed table (series matrix) and supplementary files from NCBI; the raw sequencing reads from ENA. Which of these hold counts depends on the study, so check the file list.
Paper
Ropinirole Functions Through a Dopamine Receptor D2-Independent Mechanism to Ameliorate Amyotrophic Lateral Sclerosis Phenotypes in TARDBP-Mutant iPSC-Derived Motor NeuronsJournal of neurochemistry · 2025
Summary (written by the submitters)
Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease characterized by motor neuron (MN) degeneration. The dopamine D2 receptor (D2R, DRD2) agonist ropinirole hydrochloride (ROPI) constitutes a potential therapeutic candidate for ALS through phenotypic screening of disease models of MNs that use patient-derived induced pluripotent stem cells (iPSCs).
Read the full summary ↓
The ROPALS trial, a phase I/II trial in patients with ALS, demonstrated the safety and efficacy of ROPI. However, the D2R antagonist and modulator only partially mitigated the suppressive effect of ROPI on the ALS phenotype, and the detailed mechanism of action of ROPI has not been fully elucidated. In this study, we investigated whether the therapeutic effects of ROPI in ALS depend on D2R. Using D2R-deficient iPSCs, we demonstrated that ROPI effectively mitigated neuronal cell death, reactive oxygen species (ROS) production, and neuronal hyperexcitation in a D2R-independent manner. Further analyses revealed that ROPI rescued aberrant RNA splicing and restored mRNA expression of mitochondrial proteins in a D2R-independent manner. Our data suggest that ROPI has not only a canonical D2R agonist effect, but also multifunctional effects that are mediated in a D2R-independent manner. Therefore, our findings may open new avenues for the development of more effective therapeutic approaches for ALS.
Published in
Ropinirole Functions Through a Dopamine Receptor D2-Independent Mechanism to Ameliorate Amyotrophic Lateral Sclerosis Phenotypes in TARDBP-Mutant iPSC-Derived Motor Neurons
Asano H, Kawaguchi T, Kato C et al. · Journal of neurochemistry 2025 · PMID 40826812 · doi:10.1111/jnc.70183
This dataset
Open GSE283507 in finder → Find more human RNA-seq datasets →
Download · which file do I need?

Direct links to NCBI and ENA, no account and no request form. Pick by what you want to do: take the small processed table to look, the supplementary files to re-analyse, or the original raw data to start over.

1 · Just have a look

Processed table

The series matrix: one table of values per sample as the submitters processed it. The smallest download, and it opens in Excel or R. Start here to see what the data look like.

Series matrix ↓
2 · Re-analyse it

Supplementary files

The count tables and other files the authors uploaded. Take only the samples you need, or the whole study as GSE283507_RAW.tar (it can run to tens of gigabytes).

All supplementary files ↗ Whole study · RAW.tar ↓
3 · Start from the raw reads

Raw sequencing reads

The original FASTQ files, straight from the sequencer, held at ENA. Large, and you align them yourself, so only choose this if you need to re-process the study from scratch.

Raw reads on ENA ↗

What the files usually look like: For RNA-seq the counts are usually a table among the supplementary files (look for 'counts', 'expression', 'FPKM' or 'TPM' in the file name). The series matrix of a sequencing study is sometimes nearly empty.

Also filed as BioProject PRJNA1194128 and SRA study SRP549379. Searching any of these in the dataset finder brings you back here.

NCBI GEO page ↗ Paper (PMID 40826812) ↗
Study design
18 conditions, mostly in triplicate
RC802DMSO6H-biol ×3 TDP43DMSO6H-biol ×3 TD-KODMSO6H-biol ×3 RC802ROPI6H-biol ×3 TDP43ROPI6H-biol ×3 TD-KOROPI6H-biol ×3 RC802DMSO36H-biol ×3 TDP43DMSO36H-biol ×3 +10 more

Supports a between-group comparison across 54 samples.

How we read this: 18 replicated groups read from 54 sample titles; they account for 54 of them. These groups are guessed from the sample names, not taken from the paper, so check them against the sample list below before relying on them.

Samples in this study

+ 14 more — browse all 54 samples with per-sample file links →

Datasets on a similar topic

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