ArticleHuman molecular genetics2014
Methylene blue upregulates Nrf2/ARE genes and prevents tau-related neurotoxicity.
Article in Human molecular genetics, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 71 papers.
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Who cites it
71 citing papers in PubMed, 153 citations in OpenAlex.
- Concentration-Dependent Activity of Hydromethylthionine on Clinical Decline and Brain Atrophy in a Randomized Controlled Trial in Behavioral Variant Frontotemporal Dementia.Journal of Alzheimer's disease : JAD · 2020Trial
- Concentration-Dependent Activity of Hydromethylthionine on Cognitive Decline and Brain Atrophy in Mild to Moderate Alzheimer's Disease.Journal of Alzheimer's disease : JAD · 2019Trial
- Potential of Low Dose Leuco-Methylthioninium Bis(Hydromethanesulphonate) (LMTM) Monotherapy for Treatment of Mild Alzheimer's Disease: Cohort Analysis as Modified Primary Outcome in a Phase III Clinical Trial.Journal of Alzheimer's disease : JAD · 2018Trial
- Article
- Pretreatment With Methylene Blue Atenuates Seizures, Cognitive Impairment, Hippocampal Neuronal Damage and Oxidative Stress in Pentylenetetrazole-Kindled Rats.Molecular neurobiology · 2026Article
- Methylene Blue for Prevention of Perioperative Neurocognitive Disorders: Mechanisms and Recent Clinical Evidence.Drug design, development and therapy · 2026Review
- Synergistic Neuroprotection in Tauopathic Mice via Green-Synthesized Silver Nanoparticles Co-delivering Methylene Blue and Moringa oleifera.Molecular neurobiology · 2025Article
- Methylene Blue Attenuates 3-Nitropropionic Acid-Induced Oxidative Stress and Mitochondrial Dysfunction in Striatal Cells: Therapeutic Implications in Huntington's Disease Neuropathology.International journal of molecular sciences · 2025Article
- Twenty years of therapeutic development in tauopathy mouse models: a scoping review.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2025Article
- Benfotiamine Ameliorates Streptozotocin-Induced Alzheimer's Disease in Rats by Modulating Neuroinflammation, Oxidative Stress, and Microglia.Molecular neurobiology · 2025Article
- Targeting the Electron Transport System for Enhanced Longevity.Biomolecules · 2025Review
- Model organisms for investigating the functional involvement of NRF2 in non-communicable diseases.Redox biology · 2025Review
- Targeted autophagic clearance of Tau protects against Alzheimer's disease through amelioration of Tau-mediated lysosomal stress.Theranostics · 2025Article
- Pathophysiological Aspects and Therapeutic Armamentarium of Alzheimer's Disease: Recent Trends and Future Development.Cellular and molecular neurobiology · 2023Review
- Slingshot homolog-1-mediated Nrf2 sequestration tips the balance from neuroprotection to neurodegeneration in Alzheimer's disease.Proceedings of the National Academy of Sciences of the United States of America · 2023Article
- Methylene Blue Induces Antioxidant Defense and Reparation of Mitochondrial DNA in a Nrf2-Dependent Manner during Cisplatin-Induced Renal Toxicity.International journal of molecular sciences · 2023Article
- Activators of Nrf2 to Counteract Neurodegenerative Diseases.Antioxidants (Basel, Switzerland) · 2023Review
- The Role of the Transcription Factor Nrf2 in Alzheimer's Disease: Therapeutic Opportunities.Biomolecules · 2023Review
- Molecular Mechanisms of the Protective Effects of Olive Leaf Polyphenols against Alzheimer's Disease.International journal of molecular sciences · 2023Review
- Article
11 more citing papers are in PubMed but not listed here.
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Authors and funding
15 authors at 6 institutions in 3 countries.
Funding
Abstract
Methylene blue (MB, methylthioninium chloride) is a phenothiazine that crosses the blood brain barrier and acts as a redox cycler. Among its beneficial properties are its abilities to act as an antioxidant, to reduce tau protein aggregation and to improve energy metabolism. These actions are of particular interest for the treatment of neurodegenerative diseases with tau protein aggregates known as tauopathies. The present study examined the effects of MB in the P301S mouse model of tauopathy. Both 4 mg/kg MB (low dose) and 40 mg/kg MB (high dose) were administered in the diet ad libitum from 1 to 10 months of age. We assessed behavior, tau pathology, oxidative damage, inflammation and numbers of mitochondria. MB improved the behavioral abnormalities and reduced tau pathology, inflammation and oxidative damage in the P301S mice. These beneficial effects were associated with increased expression of genes regulated by NF-E2-related factor 2 (Nrf2)/antioxidant response element (ARE), which play an important role in antioxidant defenses, preventing protein aggregation, and reducing inflammation. The activation of Nrf2/ARE genes is neuroprotective in other transgenic mouse models of neurodegenerative diseases and it appears to be an important mediator of the neuroprotective effects of MB in P301S mice. Moreover, we used Nrf2 knock out fibroblasts to show that the upregulation of Nrf2/ARE genes by MB is Nrf2 dependent and not due to secondary effects of the compound. These findings provide further evidence that MB has important neuroprotective effects that may be beneficial in the treatment of human neurodegenerative diseases with tau pathology.
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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.