ArticleProceedings of the National Academy of Sciences of the United States of America2026
DIRAS2 modulates MAPK pathway-mediated ferroptosis to regulate excitation/inhibition balance and seizure susceptibility.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
2 citing papers in PubMed.
- DIRAS2 as a key intermediate molecule joining with ferroptosis and neuronal excitation/inhibition (E/I) balance in epilepsy.Genes & diseases · 2027Article
- Advances in ferroptosis and cuproptosis: implications for spinal cord injury.Molecular biology reports · 2026Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
14 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Epilepsy is a common neurological disorder that is widely believed to be associated with an imbalance between neuronal excitation and inhibition (E/I). DIRAS2, a Ras-related GTPase, has not been well understood regarding its role and function within the nervous system. In this study, we found that DIRAS2 is downregulated in the hippocampus during the epileptogenesis phase in a kainic acid-induced epilepsy model, while it is upregulated during the chronic phase in this epilepsy model and in patients with temporal lobe epilepsy. Overexpression of DIRAS2 alleviates epileptic seizure susceptibility and activity, whereas knockdown of DIRAS2 has an opposite effect. Whole-cell patch-clamp recordings reveal that DIRAS2 reduces the neuronal E/I ratio and alleviates neuronal hyperexcitability. Mechanistically, quantitative proteomic analysis reveals that ferroptosis is involved in mediating the effects of DIRAS2. Knockdown of DIRAS2 can exacerbate ferroptosis, while overexpression protects against ferroptosis in both in vivo and in vitro studies. Ferrostatin-1, a ferroptosis inhibitor, can rescue the E/I imbalance and epileptic behavioral changes induced by DIRAS2 knockdown. Finally, we found that DIRAS2 regulates ferroptosis by inhibiting the extracellular signal-regulated kinase/p38 mitogen-activated protein kinase pathway in epileptic mice. In summary, our study demonstrates the role of DIRAS2 in epilepsy and provides a potential target for epilepsy treatment.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.