ArticleJournal of the American Heart Association2021
Activation of the ATF6 (Activating Transcription Factor 6) Signaling Pathway in Neurons Improves Outcome After Cardiac Arrest in Mice.
Article in Journal of the American Heart Association, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers, 1 of them a synthesis that pooled it.
What it found
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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.
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Who cites it
27 citing papers in PubMed, 1 synthesis or guideline pooled it, 38 citations in OpenAlex.
- Hypoxic-Ischemic Encephalopathy: Pathogenesis and Promising Therapies.Molecular neurobiology · 2025Pooled it
- Review
- Organelle regulation of SUMOylation: regulatory mechanisms and therapeutic application.Journal of advanced research · 2026Review
- Activation of Intestinal Mast Cells Contributes to Gut Damage After Cardiac Arrest in Mice.Shock (Augusta, Ga.) · 2026Article
- Activation of ATF6 Signaling Confers Long-Term Beneficial Effects in Young and Aged Mice After Permanent Stroke.Translational stroke research · 2025Article
- Environmental adversity, endoplasmic reticulum stress, and neurogenesis.Neurotoxicology · 2025Review
- AA147 Alleviates Symptoms in a Mouse Model of Multiple Sclerosis by Reducing Oligodendrocyte Loss.Glia · 2025Article
- Single-Cell Analysis in Cerebrovascular Research: Primed for Breakthroughs and Clinical Impact.Stroke · 2025Review
- Homeostasis control in health and disease by the unfolded protein response.Nature reviews. Molecular cell biology · 2025Review
- Review
- Cerebral ischemia-reperfusion injury: mechanisms and promising therapies.Frontiers in pharmacology · 2025Review
- Endothelial Unfolded Protein Response-Mediated Cytoskeletal Effects.Cell biochemistry and function · 2024Review
- The ER Stress Induced in Human Neuroblastoma Cells Can Be Reverted by Lumacaftor, a CFTR Corrector.Current issues in molecular biology · 2024Article
- Neuroprotective Approaches for Brain Injury After Cardiac Arrest: Current Trends and Prospective Avenues.Journal of stroke · 2024Review
- Inhibition of OGFOD1 by FG4592 confers neuroprotection by activating unfolded protein response and autophagy after ischemic stroke.Journal of translational medicine · 2024Article
- Involvement of Proteasomal and Endoplasmic Reticulum Stress in Neurodegeneration After Global Brain Ischemia.Molecular neurobiology · 2023Article
- Unfolded protein response pathways in stroke patients: a comprehensive landscape assessed through machine learning algorithms and experimental verification.Journal of translational medicine · 2023Article
- Divergent Proteome Reactivity Influences Arm-Selective Activation of the Unfolded Protein Response by Pharmacological Endoplasmic Reticulum Proteostasis Regulators.ACS chemical biology · 2023Article
- Pathological implications of cellular stress in cardiovascular diseases.The international journal of biochemistry & cell biology · 2023Review
- Mouse Cardiac Arrest Model for Brain Imaging and Brain Physiology Monitoring During Ischemia and Resuscitation.Journal of visualized experiments : JoVE · 2023Article
Corrections and comments
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Authors and funding
7 authors at 2 institutions in 1 country.
Funding
Abstract
Background Ischemia/reperfusion injury impairs proteostasis, and triggers adaptive cellular responses, such as the unfolded protein response (UPR), which functions to restore endoplasmic reticulum homeostasis. After cardiac arrest (CA) and resuscitation, the UPR is activated in various organs including the brain. However, the role of the UPR in CA has remained largely unknown. Here we aimed to investigate effects of activation of the ATF6 (activating transcription factor 6) UPR branch in CA. Methods and Results Conditional and inducible sATF6-KI (short-form ATF6 knock-in) mice and a selective ATF6 pathway activator 147 were used. CA was induced in mice by KCl injection, followed by cardiopulmonary resuscitation. We first found that neurologic function was significantly improved, and neuronal damage was mitigated after the ATF6 pathway was activated in neurons of sATF6-KI mice subjected to CA/cardiopulmonary resuscitation. Further RNA sequencing analysis indicated that such beneficial effects were likely attributable to increased expression of pro-proteostatic genes regulated by ATF6. Especially, key components of the endoplasmic reticulum-associated degradation process, which clears potentially toxic unfolded/misfolded proteins in the endoplasmic reticulum, were upregulated in the sATF6-KI brain. Accordingly, the CA-induced increase in K48-linked polyubiquitin in the brain was higher in sATF6-KI mice relative to control mice. Finally, CA outcome, including the survival rate, was significantly improved in mice treated with compound 147. Conclusions This is the first experimental study to determine the role of the ATF6 UPR branch in CA outcome. Our data indicate that the ATF6 UPR branch is a prosurvival pathway and may be considered as a therapeutic target for CA.
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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.