Evidence map›Paper›PMID 36260999›Full record

ArticleCell reports2022

A systemic cell stress signal confers neuronal resilience toward oxidative stress in a Hedgehog-dependent manner.

Kyung Min Chung, Hyunha Kim, Cláudio Gouveia Roque, Ethan P McCurdy, Trang T T Nguyen, Markus D Siegelin, Jee-Yeon Hwang, Ulrich Hengst

Abstract read
In one paragraph

Article in Cell reports, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.

0numbers the graph read from it
0cells of the map it votes in
11citing papers in PubMed
–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. Article
  2. Oxidation-derived metabolites sustain the antioxidant network of quercetin.Journal of computer-aided molecular design · 2026
    Article
  3. Article
  4. Review
  5. Article
  6. Article
  7. Article
  8. Article
  9. Biological resilience in health and disease.Disease models & mechanisms · 2024
    Review
  10. Article
  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

8 authors.

Kyung Min ChungThe Taub Institute for Research on Alzheimer's Disease and the Aging Brain, Vagelos College of Physicians and Surgeons, Columbia University, New York, NY 10032, USA.
Hyunha KimDepartment of Pharmacology and Neuroscience, School of Medicine, Creighton University, Omaha, NE 68178, USA.
Cláudio Gouveia RoqueThe Taub Institute for Research on Alzheimer's Disease and the Aging Brain, Vagelos College of Physicians and Surgeons, Columbia University, New York, NY 10032, USA.
Ethan P McCurdyIntegrated Program in Cellular, Molecular, and Biomedical Studies, Vagelos College of Physicians and Surgeons, Columbia University, New York, NY 10032, USA.
Trang T T NguyenDepartment of Pathology and Cell Biology, Vagelos College of Physicians and Surgeons, Columbia University, New York, NY 10032, USA.
Markus D SiegelinDepartment of Pathology and Cell Biology, Vagelos College of Physicians and Surgeons, Columbia University, New York, NY 10032, USA.
Jee-Yeon HwangDepartment of Pharmacology and Neuroscience, School of Medicine, Creighton University, Omaha, NE 68178, USA. Electronic address: jeeyeonhwang@creighton.edu.
Ulrich HengstThe Taub Institute for Research on Alzheimer's Disease and the Aging Brain, Vagelos College of Physicians and Surgeons, Columbia University, New York, NY 10032, USA; Department of Pathology and Cell Biology, Vagelos College of Physicians and Surgeons, Columbia University, New York, NY 10032, USA. Electronic address: uh2112@cumc.columbia.edu.

Funding

Translational Imaging and Behavioral Assessment (TIBA) CoreP20GM130447 · NIGMS · UNIVERSITY OF NEBRASKA MEDICAL CENTER · PI Anna Dunaevsky · 2020 to 2026
$20.7M
Neuroprotection by a Secreted Component of the Cellular Stress ResponseR01NS121337 · NINDS · COLUMBIA UNIVERSITY HEALTH SCIENCES · PI Ulrich Hengst · 2022 to 2026
$3.0M
A transcription factor complex specifically induced in neurodegenerationR01NS109607 · NINDS · COLUMBIA UNIVERSITY HEALTH SCIENCES · PI HENGST, ULRICH · 2018 to 2022
$2.3M
NIGMS NIH HHS P20 GM130447NINDS NIH HHS R01 NS109607NINDS NIH HHS R01 NS121337
6 · The paper itself

Abstract

Cells possess several conserved adaptive mechanisms to respond to stress. Stress signaling is initiated to reestablish cellular homeostasis, but its effects on the tissue or systemic levels are far less understood. We report that the secreted luminal domain of the endoplasmic reticulum (ER) stress transducer CREB3L2 (which we name TAILS [transmissible activator of increased cell livability under stress]) is an endogenous, cell non-autonomous activator of neuronal resilience. In response to oxidative insults, neurons secrete TAILS, which potentiates hedgehog signaling through direct interaction with Sonic hedgehog (SHH) and its receptor PTCH1, leading to improved antioxidant signaling and mitochondrial function in neighboring neurons. In an in vivo model of ischemic brain injury, administration of TAILS enables survival of CNS neurons and fully preserves cognitive function in behavioral tests. Our findings reveal an SHH-mediated, cell non-autonomous branch of cellular stress signaling that confers resilience to oxidative stress in the mature brain, providing protection from ischemic neurodegeneration.

Indexed as

AntioxidantsHedgehog ProteinsNeuronsOxidative StressSignal TransductionAntioxidantsHedgehog Proteinscell stress signalingCP: NeuroscienceCREB3L2global ischemiahedgehog pathwaymitochondrianeurodegenerationneuronal resilienceoxidative stress

Identifiers

PMID36260999
PMCPMC9623505

What OpenQuestion holds

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Registered trials

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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.