Evidence map›Paper›PMID 40460555›Full record

ArticleRedox biology2025

Autophagy hub-protein p62 orchestrates oxidative, endoplasmic reticulum stress, and inflammatory responses post-ischemia, exacerbating stroke outcome.

Xingyun Quan, Yukun Yang, Xiaolong Liu, Britta Kaltwasser, Matthias Pillath-Eilers, Bernd Walkenfort, Sylvia Voortmann, Ayan Mohamud Yusuf, Nina Hagemann, Chen Wang and 3 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Redox biology, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
11citing papers in PubMed, 1 pooled it
–field-weighted citation impact
1 · What the graph read from it

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.

2 · The registry

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.

3 · Its place in the literature

Who cites it

11 citing papers in PubMed, 1 synthesis or guideline pooled it.

  1. Pooled it
  2. Article
  3. Article
  4. Article
  5. Review
  6. Article
  7. Recent insights into HSP70: proteostasis and beyond.Frontiers in molecular biosciences · 2026
    Review
  8. Article
  9. Review
  10. Review
  11. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

13 authors.

Xingyun QuanDepartment of Neurology, University Hospital Essen, University of Duisburg-Essen, Germany.
Yukun YangDepartment of Neurology, University Hospital Essen, University of Duisburg-Essen, Germany.
Xiaolong LiuDepartment of Neurology, University Hospital Essen, University of Duisburg-Essen, Germany.
Britta KaltwasserDepartment of Neurology, University Hospital Essen, University of Duisburg-Essen, Germany.
Matthias Pillath-EilersDepartment of Neurology, University Hospital Essen, University of Duisburg-Essen, Germany.
Bernd WalkenfortImaging Center Essen, Institute of Experimental Immunology and Imaging, University Hospital Essen, University Duisburg-Essen, Germany.
Sylvia VoortmannImaging Center Essen, Institute of Experimental Immunology and Imaging, University Hospital Essen, University Duisburg-Essen, Germany.
Ayan Mohamud YusufDepartment of Neurology, University Hospital Essen, University of Duisburg-Essen, Germany.
Nina HagemannDepartment of Neurology, University Hospital Essen, University of Duisburg-Essen, Germany.
Chen WangDepartment of Neurology, University Hospital Essen, University of Duisburg-Essen, Germany.
Mike HasenbergImaging Center Essen, Institute of Experimental Immunology and Imaging, University Hospital Essen, University Duisburg-Essen, Germany.
Dirk M HermannDepartment of Neurology, University Hospital Essen, University of Duisburg-Essen, Germany. Electronic address: dirk.hermann@uk-essen.de.
Ulf BrockmeierDepartment of Neurology, University Hospital Essen, University of Duisburg-Essen, Germany. Electronic address: ulf.brockmeier@uk-essen.de.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Autophagy has crucial roles for ischemia/reperfusion (I/R) injury. To define the role of the autophagy hub protein p62/SQSTM1 in I/R injury, we conducted gain-of-function and loss-of-function experiments in a set of cell types, including two neuron-like cell lines, primary neurons, brain endothelial and astroglial-like cells, which we combined with mouse ischemic stroke studies. p62 levels post-I/R increased alongside intracellular ROS changes. p62 overexpression increased and p62 knockdown or pharmacological deactivation reduced I/R injury. Autophagic flux was p62-dependent, but oxygen-independent. Using p62 domain deletion mutants we identified p62's ZZ domain as key factor mediating autophagy and cell death. Death-promoting effects of p62 involved elevated ROS burden. At the same time, p62 activated a broad network of cytoprotective responses, which included NRF2-associated antioxidant signaling and inhibition of the pro-inflammatory NFκB pathway, which were bidirectionally linked with p62, and downregulation of the ER stress sensor BiP/GRP78 with consecutive activation of the UPR PERK branch. Our study establishes p62 as a master regulator of I/R injury, which offers itself as target for stroke therapies.

Indexed as

AutophagyBrain IschemiaEndoplasmic Reticulum StressInflammationOxidative StressReperfusion InjurySequestosome-1 ProteinStrokeAnimalsDisease Models, AnimalEndoplasmic Reticulum Chaperone BiPHumansMiceReactive Oxygen SpeciesEndoplasmic Reticulum Chaperone BiPHSPA5 protein, humanHspa5 protein, mouseReactive Oxygen SpeciesSequestosome-1 ProteinSqstm1 protein, mouseApoptosisMiddle cerebral artery occlusionNecroptosisNuclear factor erythroid-2-related factor-2Nuclear factor-kBOxygen-glucose deprivationProtein kinase RNA-Like endoplasmic reticulum kinaseReactive oxygen speciesReoxygenationStress signaling

Identifiers

PMID40460555
PMCPMC12167074

What Socratic holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

None linked

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 Socratic graph.