ArticlePloS one2014
Inhibition of GADD34, the stress-inducible regulatory subunit of the endoplasmic reticulum stress response, does not enhance functional recovery after spinal cord injury.
Article in PloS one, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 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
18 citing papers in PubMed, 1 synthesis or guideline pooled it, 29 citations in OpenAlex.
- Endoplasmic Reticulum Stress in Spinal Cord Injury: Pathological Roles, Molecular Targets, and Emerging Treatments: A Systematic Review.Molecular neurobiology · 2026Pooled it
- Reduced Expression of Oligodendrocyte Linage-Enriched Transcripts During the Endoplasmic Reticulum Stress/Integrated Stress Response.ASN neuro · 2024Article
- Acute Pharmacological Inhibition of Protein Kinase R-Like Endoplasmic Reticulum Kinase Signaling After Spinal Cord Injury Spares Oligodendrocytes and Improves Locomotor Recovery.Journal of neurotrauma · 2023Article
- A systems biological analysis of the ATF4-GADD34-CHOP regulatory triangle upon endoplasmic reticulum stress.FEBS open bio · 2022Article
- The Proteostasis Network: A Global Therapeutic Target for Neuroprotection after Spinal Cord Injury.Cells · 2022Review
- BZW1 Facilitates Glycolysis and Promotes Tumor Growth in Pancreatic Ductal Adenocarcinoma Through Potentiating eIF2α Phosphorylation.Gastroenterology · 2022Article
- Targeting Endoplasmic Reticulum Stress as an Effective Treatment for Alcoholic Pancreatitis.Biomedicines · 2022Review
- The impact of stress on the transcriptomic signature of iNKT1 cells.Biochemistry and biophysics reports · 2021Article
- Induction of the integrated stress response in the rat cornea.Experimental eye research · 2021Article
- Article
- Unfolded protein response in myelin disorders.Neural regeneration research · 2020Review
- TFE3, a potential therapeutic target for Spinal Cord Injury via augmenting autophagy flux and alleviating ER stress.Theranostics · 2020Article
- Methotrexate remediates spinal cord injuryExperimental and therapeutic medicine · 2018Article
- Guanabenz promotes neuronal survival via enhancement of ATF4 and parkin expression in models of Parkinson disease.Experimental neurology · 2018Article
- ER stress and the unfolded protein response in neurodegeneration.Nature reviews. Neurology · 2017Review
- Integrated Stress Response as a Therapeutic Target for CNS Injuries.BioMed research international · 2017Review
- Guanabenz Prevents d-Galactosamine/Lipopolysaccharide-Induced Liver Damage and Mortality.Frontiers in immunology · 2017Article
- Activation of the unfolded protein response promotes axonal regeneration after peripheral nerve injury.Scientific reports · 2016Article
Corrections and comments
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
Abstract
Activation of the endoplasmic reticulum stress response (ERSR) is a hallmark of various pathological diseases and/or traumatic injuries. Restoration of ER homeostasis can contribute to improvement in the functional outcome of these diseases. Using genetic and pharmacological inhibition of the PERK-CHOP arm of the ERSR, we recently demonstrated improvements in hindlimb locomotion after spinal cord injury (SCI) and implicated oligodendrocyte survival as a potential mechanism. Here, we investigated the contribution of stress-inducible PPP1R15A/GADD34, an ERSR signaling effector downstream of CHOP that dephosphorylates eIF2α, in the pathogenesis of SCI. We show that although genetic ablation of GADD34 protects oligodendrocyte precursor cells (OPCs) against ER stress-mediated cell death in vitro and results in differential ERSR attenuation in vivo after SCI, there is no improvement in hindlimb locomotor function. Guanabenz, a FDA approved antihypertensive drug, was recently shown to reduce the burden of misfolded proteins in the ER by directly targeting GADD34. Guanabenz protected OPCs from ER stress-mediated cell death in vitro and attenuated the ERSR in vivo after SCI. However, guanabenz administration failed to rescue the locomotor deficits after SCI. These data suggest that deletion of GADD34 alone is not sufficient to improve functional recovery after SCI.
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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.