ArticleAutophagy2012
Methylthioninium chloride (methylene blue) induces autophagy and attenuates tauopathy in vitro and in vivo.
Article in Autophagy, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 156 papers, 1 of them a synthesis that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
156 citing papers in PubMed, 1 synthesis or guideline pooled it, 296 citations in OpenAlex.
- Nutraceutical Approaches of Autophagy and Neuroinflammation in Alzheimer's Disease: A Systematic Review.Molecules (Basel, Switzerland) · 2020Pooled it
- 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
- Tau physiology and pathology: impacts on cellular structures and neurodegenerative diseases.Inflammopharmacology · 2026Review
- SLC38A9 Regulation Affects Hippocampal Neuronal Autophagy: A Potential Alzheimer's Therapeutic Approach by Suppressing Alzheimer's Disease-Related Protein Deposition.CNS neuroscience & therapeutics · 2026Article
- Omipalisib reduces hyperphosphorylated tau protein by modulating mTOR-autophagy pathway.PloS one · 2026Article
- Review
- Twenty years of therapeutic development in tauopathy mouse models: a scoping review.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2025Article
- Review
- (-)-Epicatechin Rescues Memory Deficits by Activation of Autophagy in a Mouse Model of Tauopathies.MedComm · 2025Article
- Therapeutic modulation of neurogenesis to improve hippocampal plasticity and cognition in aging and Alzheimer's disease.Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2025Review
- Exposure to Manganese Induces Autophagy-Lysosomal Pathway Dysfunction-Mediated Tauopathy by Activating the cGAS-STING Pathway in the Brain.Environment & health (Washington, D.C.) · 2025Article
- Cannabidiol-Induced Autophagy Ameliorates Tau Protein Clearance.Neurotoxicity research · 2025Article
- High-throughput screening identifies a novel small-molecule modulator of Hsp70 that selectively enhances ubiquitination and degradation of misfolded neuronal NO synthase.Molecular pharmacology · 2025Article
- Potential of methylene blue fluorescence angiography for multiple intraoperative tissue perfusion assessments in plastic and reconstructive surgery: current knowledge and prospects.Frontiers in surgery · 2025Article
- Hierarchical Protofilament Intertwining Rules the Formation of Mixed-Curvature Amyloid Polymorphs.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2024Article
- Multidimensional autophagy nano-regulator boosts Alzheimer's disease treatment by improving both extra/intraneuronal homeostasis.Acta pharmaceutica Sinica. B · 2024Article
- Sex differences in response to obesity and caloric restriction on cognition and hippocampal measures of autophagic-lysosomal transcripts and signaling pathways.BMC neuroscience · 2024Article
- Methotrimeprazine is a neuroprotective antiviral in JEV infection via adaptive ER stress and autophagy.EMBO molecular medicine · 2024Article
96 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
10 authors at 8 institutions in 2 countries.
Funding
Abstract
More than 30 neurodegenerative diseases including Alzheimer disease (AD), frontotemporal lobe dementia (FTD), and some forms of Parkinson disease (PD) are characterized by the accumulation of an aggregated form of the microtubule-binding protein tau in neurites and as intracellular lesions called neurofibrillary tangles. Diseases with abnormal tau as part of the pathology are collectively known as the tauopathies. Methylthioninium chloride, also known as methylene blue (MB), has been shown to reduce tau levels in vitro and in vivo and several different mechanisms of action have been proposed. Herein we demonstrate that autophagy is a novel mechanism by which MB can reduce tau levels. Incubation with nanomolar concentrations of MB was sufficient to significantly reduce levels of tau both in organotypic brain slice cultures from a mouse model of FTD, and in cell models. Concomitantly, MB treatment altered the levels of LC3-II, cathepsin D, BECN1, and p62 suggesting that it was a potent inducer of autophagy. Further analysis of the signaling pathways induced by MB suggested a mode of action similar to rapamycin. Results were recapitulated in a transgenic mouse model of tauopathy administered MB orally at three different doses for two weeks. These data support the use of this drug as a therapeutic agent in neurodegenerative diseases.
Indexed as
Identifiers
What OpenQuestion holds
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.