ArticlePloS one2015
Guanabenz Treatment Accelerates Disease in a Mutant SOD1 Mouse Model of ALS.
Article in PloS one, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 43 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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
43 citing papers in PubMed, 1 synthesis or guideline pooled it, 78 citations in OpenAlex.
- Metabolic Alteration and Amyotrophic Lateral Sclerosis Outcome: A Systematic Review.Frontiers in neurology · 2019Pooled it
- Protein misfolding, amyotrophic lateral sclerosis and guanabenz: protocol for a phase II RCT with futility design (ProMISe trial).BMJ open · 2017Trial
- Pediatric pharmacokinetics and pharmacodynamics of guanabenz for the treatment of vanishing white matter.Scientific reports · 2026Article
- Sephin1 reduces TDP-43 cytoplasmic mislocalization and improves motor neuron survival in ALS models.Life science alliance · 2025Article
- Dual Nature of Mitochondrial Integrated Stress Response: Molecular Switches from Protection to Pathology.Genes · 2025Review
- Kaempferol enhances ER-mitochondria coupling and protects motor neurons from mitochondrial dysfunction and ER stress in C9ORF72-ALS.Acta neuropathologica communications · 2025Article
- Predicting cellular adaptation proteins dependent on eIF2α regulation under stress conditions: Physiological and pathophysiological implications in neuronal function.Computational and structural biotechnology journal · 2025Article
- Mammalian integrated stress responses in stressed organelles and their functions.Acta pharmacologica Sinica · 2024Review
- PERK modulation, with GSK2606414, Sephin1 or salubrinal, failed to produce therapeutic benefits in the SOD1G93A mouse model of ALS.PloS one · 2024Article
- CDNF rescues motor neurons in models of amyotrophic lateral sclerosis by targeting endoplasmic reticulum stress.Brain : a journal of neurology · 2023Article
- Geometric Isomer of Guanabenz Confers Hepatoprotection to a Murine Model of Acetaminophen Toxicity.Chemical research in toxicology · 2023Article
- Guanabenz ameliorates disease in vanishing white matter mice in contrast to sephin1.Annals of clinical and translational neurology · 2022Article
- The Role and Therapeutic Potential of the Integrated Stress Response in Amyotrophic Lateral Sclerosis.International journal of molecular sciences · 2022Review
- Protein synthesis modulation as a therapeutic approach for amyotrophic lateral sclerosis and frontotemporal dementia.Neural regeneration research · 2022Review
- Pharmacological targeting of endoplasmic reticulum stress in disease.Nature reviews. Drug discovery · 2022Review
- Towards Understanding the Relationship Between ER Stress and Unfolded Protein Response in Amyotrophic Lateral Sclerosis.Frontiers in aging neuroscience · 2022Review
- UsingFrontiers in pharmacology · 2022Review
- The Unfolded Protein Responses in Health, Aging, and Neurodegeneration: Recent Advances and Future Considerations.Frontiers in molecular neuroscience · 2022Review
- PERK Pathway and Neurodegenerative Disease: To Inhibit or to Activate?Biomolecules · 2021Review
- Endoplasmic Reticulum Stress-Associated Neuronal Death and Innate Immune Response in Neurological Diseases.Frontiers in immunology · 2021Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
14 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease characterized by loss of motor neurons. The mechanisms leading to motor neuron degeneration in ALS are unclear. However, there is evidence for involvement of endoplasmic reticulum (ER) stress and the unfolded protein response (UPR) in ALS, notably in mutant SOD1 mediated models of ALS. Stress induced phosphorylation of the eIF2 alpha subunit by eukaryotic translation initiation factor 2-alpha kinase 3 Perk activates the UPR. Guanabenz is a centrally acting alpha2 adrenergic receptor agonist shown to interact with a regulatory subunit of the protein phosphatase, Pp1/Gadd34, and selectively disrupt the dephosphorylation of the alpha subunit of eukaryotic initiation factor 2 (eif2alpha). Here we demonstrate that guanabenz is protective in fibroblasts expressing G93A mutant SOD1 when they are exposed to tunicamycin mediated ER stress. However, in contrast to other reports, guanabenz treatment accelerated ALS-like disease progression in a strain of mutant SOD1 transgenic ALS mice. This study highlights challenges of pharmacological interventions of cellular stress responses in whole animal models of ALS.
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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.