ArticleCNS neuroscience & therapeutics2026
Sestrin2 Mitigates Neuronal Ferroptosis Following Subarachnoid Hemorrhage via Orchestration of the AMPK/PGC1α/Nrf2 Signaling Axis.
Article in CNS neuroscience & therapeutics, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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
0 citing papers in PubMed.
No citing paper in PubMed yet.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
10 authors.
Funding
Abstract
backgroundEarly brain injury after subarachnoid hemorrhage (SAH) involves oxidative stress and ferroptosis. Sestrin2 (SESN2) regulates redox homeostasis, but its role in SAH-induced ferroptosis remains unclear.
methodsSAH was induced by internal carotid puncture; HT22 cells were hemin-treated. We assessed neurological deficits, brain edema, BBB integrity, iron levels, mitochondrial ultrastructure, and ferroptosis and signaling proteins by Western blot and immunofluorescence. SESN2 function was probed using knockdown, recombinant human SESN2 (rh-SESN2), and pathway inhibitors.
resultsrh-SESN2 improved neurological outcomes, attenuated iron accumulation, and preserved mitochondrial morphology after SAH. In HT22 cells, rh-SESN2 increased viability, decreased ROS and MDA, and partially restored SOD activity. rh-SESN2 upregulated GPX4, SLC7A11, and Nrf2 and its nuclear translocation, whereas SESN2 knockdown exacerbated ferroptosis and reduced these proteins. Mechanistically, SESN2 activated AMPK and upregulated PGC1α, facilitating Nrf2 nuclear translocation and inducing antiferroptotic proteins. Pathway inhibition established an AMPK/PGC1α/Nrf2 hierarchy: AMPK inhibition suppressed PGC1α and Nrf2 activation, PGC1α inhibition reduced Nrf2 translocation, and ML385 abrogated SESN2's protective effects.
conclusionSESN2 activates AMPK, which in turn upregulates PGC1α and promotes Nrf2 nuclear translocation, ultimately inhibiting neuronal ferroptosis after SAH. Targeting this AMPK/PGC1α/Nrf2 axis may provide a novel therapeutic approach for post-SAH neuroprotection.
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.