ArticleJournal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism2021
Inhibition of eIF5A hypusination pathway as a new pharmacological target for stroke therapy.
Article in Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
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Who cites it
15 citing papers in PubMed, 29 citations in OpenAlex.
- Mitochondria serve as a holdout compartment for aggregation-prone proteins hindering efficient degradation.Nature communications · 2026Article
- Overcoming resistance to arginine deprivation therapy using GC7 in pleural mesothelioma.iScience · 2025Article
- Enhancing Solubility and Bioefficacy of Stilbenes by Liposomal Encapsulation-The Case of Macasiamenene F.ACS omega · 2024Article
- Arginine metabolism regulates human erythroid differentiation through hypusination of eIF5A.Blood · 2023Article
- Article
- Receptor for Advanced Glycation End Product, Organ Crosstalk, and Pathomechanism Targets for Comprehensive Molecular Therapeutics in Diabetic Ischemic Stroke.Biomolecules · 2022Review
- Metabolic Pathways ofPharmaceutics · 2022Review
- Functional Assessment of Stroke-Induced Regulation of miR-20a-3p and Its Role as a Neuroprotectant.Translational stroke research · 2022Article
- Role of eIF5A in Mitochondrial Function.International journal of molecular sciences · 2022Review
- The eukaryotic initiation factor 5A (eIF5A1), the molecule, mechanisms and recent insights into the pathophysiological roles.Cell & bioscience · 2021Review
- Akt Inhibition as Preconditioning Treatment to Protect Kidney Cells against Anoxia.International journal of molecular sciences · 2021Article
- Hypoxia Tolerant Species: The Wisdom of Nature Translated into Targets for Stroke Therapy.International journal of molecular sciences · 2021Review
- Iron in Translation: From the Beginning to the End.Microorganisms · 2021Review
- Inhibition of eIF5A hypusination reprogrammes metabolism and glucose handling in mouse kidney.Cell death & disease · 2021Article
- Yeast Translation Elongation Factor eIF5A Expression Is Regulated by Nutrient Availability through Different Signalling Pathways.International journal of molecular sciences · 2020Article
Corrections and comments
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Authors and funding
7 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
In eukaryotes, the polyamine pathway generates spermidine that activates the hypusination of the translation factor eukaryotic initiation factor 5A (eIF5A). Hypusinated-eIF5A modulates translation, elongation, termination and mitochondrial function. Evidence in model organisms like drosophila suggests that targeting polyamines synthesis might be of interest against ischemia. However, the potential of targeting eIF5A hypusination in stroke, the major therapeutic challenge specific to ischemia, is currently unknown. Using in vitro models of ischemic-related stress, we documented that GC7, a specific inhibitor of a key enzyme in the eIF5A activation pathway, affords neuronal protection. We identified the preservation of mitochondrial function and thereby the prevention of toxic ROS generation as major processes of GC7 protection. To represent a thoughtful opportunity of clinical translation, we explored whether GC7 administration reduces the infarct volume and functional deficits in an in vivo transient focal cerebral ischemia (tFCI) model in mice. A single GC7 pre- or post-treatment significantly reduces the infarct volume post-stroke. Moreover, GC7-post-treatment significantly improves mouse performance in the rotarod and Morris water-maze, highlighting beneficial effects on motor and cognitive post-stroke deficits. Our results identify the targeting of the polyamine-eIF5A-hypusine axis as a new therapeutic opportunity and new paradigm of research in stroke and ischemic diseases.
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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.