ArticleFrontiers in molecular neuroscience2020
Metformin Protects From Rotenone-Induced Nigrostriatal Neuronal Death in Adult Mice by Activating AMPK-FOXO3 Signaling and Mitigation of Angiogenesis.
Article in Frontiers in molecular neuroscience, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It has been retracted, and should not be counted. Cited by 32 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.
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Who cites it
32 citing papers in PubMed, 65 citations in OpenAlex.
- Impact of metformin use on neurocognitive functions in older people: a systematic review and meta-analysis.Dementia & neuropsychologia · 2026Review
- From Diabetes to Degenerative Diseases: The Multifaceted Action of Metformin.International journal of molecular sciences · 2025Review
- Overview of Metformin and Neurodegeneration: A Comprehensive Review.Pharmaceuticals (Basel, Switzerland) · 2025Review
- Mechanism and Clinical Application Prospects of Mitochondrial DNA Single Nucleotide Polymorphism in Neurodegenerative Diseases.Neurochemical research · 2024Review
- Neuroprotective Effect of Maresin-1 in Rotenone-Induced Parkinson's Disease in Rats: The Putative Role of the JAK/STAT Pathway.Neurochemical research · 2024Article
- Evaluation of Neuroprotective Effect of Gut Microbe in Parkinson's Disease: An In Silico and In Vivo Approach.Neuromolecular medicine · 2024Article
- Identification of Parkinson's disease PACE subtypes and repurposing treatments through integrative analyses of multimodal data.NPJ digital medicine · 2024Article
- Novel and experimental therapeutics for the management of motor and non-motor Parkinsonian symptoms.Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology · 2024Review
- In Vivo Study ofPlants (Basel, Switzerland) · 2024Article
- AMPK Signaling Pathway as a Potential Therapeutic Target for Parkinson's Disease.Advanced pharmaceutical bulletin · 2024Review
- Chitosan-coated nanostructured lipid carriers for effective brain delivery of Tanshinone IIA in Parkinson's disease: interplay between nuclear factor-kappa β and cathepsin B.Drug delivery and translational research · 2024Article
- Mito-metformin protects against mitochondrial dysfunction and dopaminergic neuronal degeneration by activating upstream PKD1 signaling in cell culture and MitoPark animal models of Parkinson's disease.Frontiers in neuroscience · 2024Article
- Neurodegenerative Proteinopathies Induced by Environmental Pollutants: Heat Shock Proteins and Proteasome as Promising Therapeutic Tools.Pharmaceutics · 2023Review
- AMPK-dependent autophagy activation and alpha-Synuclein clearance: a putative mechanism behind alpha-mangostin's neuroprotection in a rotenone-induced mouse model of Parkinson's disease.Metabolic brain disease · 2022Article
- Association between Parkinson's Disease and Diabetes Mellitus: From Epidemiology, Pathophysiology and Prevention to Treatment.Aging and disease · 2022Article
- Hibiscetin attenuates oxidative, nitrative stress and neuroinflammation via suppression of TNF-α signaling in rotenone induced parkinsonism in rats.Saudi pharmaceutical journal : SPJ : the official publication of the Saudi Pharmaceutical Society · 2022Article
- Parkinson's Disease and Sugar Intake-Reasons for and Consequences of a Still Unclear Craving.Nutrients · 2022Review
- Actions of Metformin in the Brain: A New Perspective of Metformin Treatments in Related Neurological Disorders.International journal of molecular sciences · 2022Review
- Metformin in nucleus accumbens core reduces cue-induced cocaine seeking in male and female rats.Addiction biology · 2022Article
- Anti-inflammatory, Antioxidant, and Antiapoptotic Action of Metformin Attenuates Ethanol Neurotoxicity in the Animal Model of Fetal Alcohol Spectrum Disorders.Neurotoxicity research · 2022Article
Corrections and comments
- Retraction · 2026-01-12Duplication of/in Image · Euphemisms for Duplication · Investigation by Journal/Publisher · Investigation by Third Party · Objections by Author(s) · Unreliable Data · Unreliable Results and/or Conclusions · · See also: https://pubpeer.com/publications/0CB291A7A54111D06BA251DBC3E314
- Retracted
Authors and funding
7 authors at 5 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Parkinson's disease (PD) is a neurodegenerative disease that affects substantia nigra dopamine neurons. Many studies have documented the role of oxidative stress and angiogenesis in the pathogenesis of PD. Metformin (MTF) is an antidiabetic medication and AMP-activated protein kinase (AMPK) regulator that has shown antioxidant and antiangiogenic properties in many disorders. The aim of this study is to investigate the neuroprotective effect of MTF in a mouse model of rotenone-prompted PD with a highlight on its influence on the AMPK/forkhead box transcription factor O3 (FOXO3) pathway and striatal angiogenesis. In the running study, PD was induced in mice using repeated doses of rotenone and concomitantly treated with MTF 100 or 200 mg/kg/day for 18 days. Rotarod and pole tests were used to examine the animals' motor functionality. After that, animals were sacrificed, and brains were isolated and processed for immunohistochemical investigations or biochemical analyses. Oxidant stress and angiogenic markers were measured, including reduced glutathione, malondialdehyde, the nuclear factor erythroid 2-related factor 2 (Nrf2), hemoxygenase-1, thioredoxin, AMPK, FOXO3, and vascular endothelial growth factor (VEGF). Results indicated that MTF improved animals' motor function, improved striatal glutathione, Nrf2, hemoxygenase-1, and thioredoxin. Furthermore, MTF upregulated AMPK-FOXO3 proteins and reduced VEGF and cleaved caspase 3. MTF also increased the number of tyrosine hydroxylase (TH)-stained neurons in the substantia nigra neurons and in striatal neuronal terminals. This study is the first to highlight that the neuroprotective role of MTF is mediated through activation of AMPK-FOXO3 signaling and inhibition of the proangiogenic factor, VEGF. Further studies are warranted to confirm this mechanism in other models of PD and neurodegenerative 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.