ArticlePloS one2012
Exendin-4 ameliorates motor neuron degeneration in cellular and animal models of amyotrophic lateral sclerosis.
Article in PloS one, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 81 papers, 1 of them a synthesis that pooled it.
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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
81 citing papers in PubMed, 1 synthesis or guideline pooled it, 130 citations in OpenAlex.
- The Role of Short-Chain Fatty Acids in Microbiota-Gut-Brain Cross-Talk with a Focus on Amyotrophic Lateral Sclerosis: A Systematic Review.International journal of molecular sciences · 2023Pooled it
- The Pleiotropic Therapeutic Perspectives of GLP-1 and GIP Receptor Agonists in Spinal Cord Injury: A Narrative Review.Molecular neurobiology · 2026Review
- The promise of GLP-1 receptor agonists for neurodegenerative diseases.The Journal of clinical investigation · 2026Review
- Targeting neuroinflammation in neurodegenerative disorders: the emerging potential of semaglutide.Inflammation research : official journal of the European Histamine Research Society ... [et al.] · 2026Review
- Dysbiosis of gut microbiota and metabolomic alterations in myasthenia gravis: insights from 16S rRNA sequencing and untargeted metabolomics.Frontiers in immunology · 2026Article
- GLP-1 Signalling as a Therapeutic Avenue in Parkinson's Disease: A Comprehensive Review.International journal of molecular sciences · 2025Review
- Engineered GLP-1R-targeting nanoplatforms: multimodal therapeutics in human diseases.Journal of nanobiotechnology · 2025Review
- From metabolism to mind: The expanding role of the GLP-1 receptor in neurotherapeutics.Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2025Review
- Targeting Sarcopenia in CKD: The Emerging Role of GLP-1 Receptor Agonists.International journal of molecular sciences · 2025Review
- Therapeutic Effects of GLP-1 Receptor Agonists and DPP-4 Inhibitors in Neuropathic Pain: Mechanisms and Clinical Implications.Biomolecules · 2025Review
- Incretin-based therapeutics for the treatment of neurodegenerative diseases.Nature metabolism · 2025Review
- Research on the effects of GLP-1 receptor agonists in treating cognitive dysfunction and gait disorders in elderly patients with diabetes.Frontiers in pharmacology · 2025Review
- The Beneficial Effects of GLP-1 Receptor Agonists Other than Their Anti-Diabetic and Anti-Obesity Properties.Medicina (Kaunas, Lithuania) · 2024Review
- Semaglutide Ameliorates Diabetic Neuropathic Pain by Inhibiting Neuroinflammation in the Spinal Cord.Cells · 2024Article
- Exploring the Role of Metabolic Hormones in Amyotrophic Lateral Sclerosis.International journal of molecular sciences · 2024Article
- The GLP-1 receptor agonist exenatide improves recovery from spinal cord injury by inducing macrophage polarization toward the M2 phenotype.Frontiers in neuroscience · 2024Article
- The Regulation of Metabolic Homeostasis by Incretins and the Metabolic Hormones Produced by Pancreatic Islets.Diabetes, metabolic syndrome and obesity : targets and therapy · 2024Review
- Administration of the GLP-1 receptor agonist exenatide in rats improves functional recovery after spinal cord injury by reducing endoplasmic reticulum stress.IBRO neuroscience reports · 2023Article
- Article
- Multifaceted Roles of GLP-1 and Its Analogs: A Review on Molecular Mechanisms with a Cardiotherapeutic Perspective.Pharmaceuticals (Basel, Switzerland) · 2023Review
21 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
12 authors at 5 institutions in 1 country.
Funding
Abstract
Amyotrophic lateral sclerosis (ALS) is a devastating neurodegenerative disease characterized by a progressive loss of lower motor neurons in the spinal cord. The incretin hormone, glucagon-like peptide-1 (GLP-1), facilitates insulin signaling, and the long acting GLP-1 receptor agonist exendin-4 (Ex-4) is currently used as an anti-diabetic drug. GLP-1 receptors are widely expressed in the brain and spinal cord, and our prior studies have shown that Ex-4 is neuroprotective in several neurodegenerative disease rodent models, including stroke, Parkinson's disease and Alzheimer's disease. Here we hypothesized that Ex-4 may provide neuroprotective activity in ALS, and hence characterized Ex-4 actions in both cell culture (NSC-19 neuroblastoma cells) and in vivo (SOD1 G93A mutant mice) models of ALS. Ex-4 proved to be neurotrophic in NSC-19 cells, elevating choline acetyltransferase (ChAT) activity, as well as neuroprotective, protecting cells from hydrogen peroxide-induced oxidative stress and staurosporine-induced apoptosis. Additionally, in both wild-type SOD1 and mutant SOD1 (G37R) stably transfected NSC-19 cell lines, Ex-4 protected against trophic factor withdrawal-induced toxicity. To assess in vivo translation, SOD1 mutant mice were administered vehicle or Ex-4 at 6-weeks of age onwards to end-stage disease via subcutaneous osmotic pump to provide steady-state infusion. ALS mice treated with Ex-4 showed improved glucose tolerance and normalization of behavior, as assessed by running wheel, compared to control ALS mice. Furthermore, Ex-4 treatment attenuated neuronal cell death in the lumbar spinal cord; immunohistochemical analysis demonstrated the rescue of neuronal markers, such as ChAT, associated with motor neurons. Together, our results suggest that GLP-1 receptor agonists warrant further evaluation to assess whether their neuroprotective potential is of therapeutic relevance in 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.