ArticleDaru : journal of Faculty of Pharmacy, Tehran University of Medical Sciences2019
Metformin-induced AMPK activation stimulates remyelination through induction of neurotrophic factors, downregulation of NogoA and recruitment of Olig2+ precursor cells in the cuprizone murine model of multiple sclerosis.
Article in Daru : journal of Faculty of Pharmacy, Tehran University of Medical Sciences, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT05298670 (Drug Repurposing Using Metformin for Improving the Therapeutic Outcome in Multiple Sclerosis Patients), which is not on this map. Cited by 26 papers.
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.
Drug Repurposing Using Metformin for Improving the Therapeutic Outcome in Multiple Sclerosis Patients
Who cites it
26 citing papers in PubMed, 41 citations in OpenAlex.
- The impact of metformin use on the outcomes of relapse-remitting multiple sclerosis patients receiving interferon beta 1a: an exploratory prospective phase II open-label randomized controlled trial.Journal of neurology · 2024Trial
- Maternal metformin protects developing auditory brainstem function after neonatal hypoxia-ischemia in a neonatal rat model.Clinical and experimental pediatrics · 2026Article
- GPCR-Driven Muscarinic M1 and Histamine H1 Receptor Signaling Converging on the PI3K/Akt/mTOR Pathway: Functional Integration in Neuroinflammation and Myelin Repair in Multiple Sclerosis.Molecular neurobiology · 2026Review
- Antidiabetes agents and risk of incident depression in 686,522 people with type 2 diabetes mellitus: A 20-year population-based cohort study.Psychological medicine · 2026Article
- Exercise mimetics: molecular mechanisms, biological and therapeutic effects.Molecular biomedicine · 2026Review
- Metformin alters mitochondria-related metabolism and enhances human oligodendrocyte function.Nature communications · 2025Article
- Randomized, double-blind, placebo-controlled pilot study of metformin as an adjunctive therapy in Parkinson's disease.Frontiers in pharmacology · 2025Article
- The role of autophagy in the pathogenesis and treatment of multiple sclerosis.Autophagy reports · 2025Review
- Cellular senescence in Alzheimer's disease: from physiology to pathology.Translational neurodegeneration · 2024Review
- Effect of Metformin on Peripheral Nerve Morphology in Type 2 Diabetes: A Cross-Sectional Observational Study.Diabetes · 2024Observational
- Clemastine and metformin extend the window of NMDA receptor surface expression in ageing oligodendrocyte precursor cells.Scientific reports · 2024Article
- Effect of Metformin on Epidermal Neural Crest Stem Cells and Their Potential Application in Ameliorating Paclitaxel-induced Neurotoxicity Phenotype.Stem cell reviews and reports · 2024Article
- A metformin add-on clinical study in multiple sclerosis to evaluate brain remyelination and neurodegeneration (MACSiMiSE-BRAIN): study protocol for a multi-center randomized placebo controlled clinical trial.Frontiers in immunology · 2024Article
- The Roles of Caloric Restriction Mimetics in Central Nervous System Demyelination and Remyelination.Current issues in molecular biology · 2023Review
- Nerve Growth Factor and Autoimmune Diseases.Current issues in molecular biology · 2023Review
- Metformin attenuates white matter injury and cognitive impairment induced by chronic cerebral hypoperfusion.Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism · 2023Article
- Synthetic Thyroid Hormone Receptor-β Agonists Promote Oligodendrocyte Precursor Cell Differentiation in the Presence of Inflammatory Challenges.Pharmaceuticals (Basel, Switzerland) · 2023Article
- The AMPK activator metformin improves recovery from demyelination by shifting oligodendrocyte bioenergetics and accelerating OPC differentiation.Frontiers in cellular neuroscience · 2023Article
- Remyelination in Multiple Sclerosis: Findings in the Cuprizone Model.International journal of molecular sciences · 2022Review
- Wuzi Yanzong Pill relieves CPZ-induced demyelination by improving the microenvironment in the brain.Heliyon · 2022Article
Corrections and comments
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Authors and funding
8 authors at 4 institutions in 1 country.
Funding
Abstract
purposeOligodendrocytes (OLGs) damage and myelin distraction is considered as a critical step in many neurological disorders especially multiple sclerosis (MS). Cuprizone (cup) animal model of MS targets OLGs degeneration and frequently used to the mechanistic understanding of de- and remyelination. The aim of this study was exploring the effects of metformin on the OLGs regeneration, myelin repair and profile of neurotrophic factors in the mice brain after cup-induced acute demyelination.
methodsMice (C57BL/6 J) were fed with chow containing 0.2% cup for 5 weeks to induce specific OLGs degeneration and acute demyelination. Next, the cup was withdrawn to allow one-week recovery (spontaneous remyelination). At the end of this period, mature OLGs markers, myelin-associated neurite outgrowth inhibitor protein A (NogoA), premature specific OLGs transcription factor (Olig2), anti-apoptosis marker (survivin), neurotrophic factors, and AMPK activation were monitored in the presence or absence of metformin (50 mg/kg body weight/day) in the corpus callosum (CC).
resultsOur finding indicated that consumption of metformin during the recovery period potentially induced an active form of AMPK (p-AMPK) and promoted repopulation of mature OLGs (MOG
conclusionsThis study for the first time reveals that metformin-induced AMPK, a master regulator of energy homeostasis, activation following toxic demyelination could potentially accelerate regeneration and supports spontaneous demyelination. These findings suggest the development of new therapeutic strategies based on AMPK activation for MS in the near future. Graphical abstract An overview of the possible molecular mechanisms of action of metformin-mediated remyelinationa.
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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.