The DOI matches its Crossref record; 48 of the 49 references it cites were found in a registry or an index.
Methylthioninium chloride (methylene blue) induces autophagy and attenuates tauopathy in vitro and in vivo
Open accessAbstract
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.
Overview
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Verification
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
The source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“Any putative benefit attributed to methylene blue has been thought to be secondary to reduced tau fibrillization and aggregation and induction of autophagy, which leads to reduced tau pathology and neuron death in mouse models of tauopathy (Congdon et al., 2012; Crowe et al., 2013; Wischik et al., 1996).”
From Alzheimer Disease: An Update on Pathobiology and Treatment Strategies (2019) · cites this paper as Congdon et al., 2012
Experimental — accuracy not yet measured
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Citations
Cites
1 retracted
Shi, Y., Yan, H., Frost, P., Gera, J., & Lichtenstein, A. K. (2005) · Molecular Cancer Therapeutics · doi:10.1158/1535-7163.mct-05-0068 · Cited by 368
RetractedBjørkøy, G., Lamark, T., Brech, A., Outzen, H., Perander, M., Øvervatn, A., Stenmark, H., & Johansen, T. (2005) · The Journal of Cell Biology · doi:10.1083/jcb.200507002 · Cited by 3,276
Kimura, S., Noda, T., & Yoshimori, T. (2007) · Autophagy · doi:10.4161/auto.4451 · Cited by 2,278
Homeostatic levels of p62 control cytoplasmic inclusion body formation in autophagy-deficient mice.
Komatsu, M., Waguri, S., Koike, M., Sou, Y.-S., Ueno, T., Hara, T., Mizushima, N., Iwata, J.-I., Ezaki, J., Murata, S., et al. (2007) · Cell · doi:10.1016/j.cell.2007.10.035 · Cited by 2,124
Mizushima, N., Yamamoto, A., Matsui, M., Yoshimori, T., & Ohsumi, Y. (2004) · Molecular Biology of the Cell · doi:10.1091/mbc.e03-09-0704 · Cited by 2,105
Impaired Degradation of Mutant α-Synuclein by Chaperone-Mediated Autophagy
Cuervo, A. M., Stefanis, L., Fredenburg, R., Lansbury, P. T., & Sulzer, D. (2004) · Science · doi:10.1126/science.1101738 · Cited by 2,024
Lewis, J., McGowan, E., Rockwood, J., Melrose, H., Nacharaju, P., Van Slegtenhorst, M., Gwinn-Hardy, K., Murphy, M. P., Baker, M., Yu, X., et al. (2000) · Nature Genetics · doi:10.1038/78078 · Cited by 1,371
Insulin signalling to mTOR mediated by the Akt/PKB substrate PRAS40
Haar, E. V., Lee, S.-I., Bandhakavi, S., Griffin, T. J., & Kim, D. (2007) · Nature Cell Biology · doi:10.1038/ncb1547 · Cited by 1,227
Beclin 1 Forms Two Distinct Phosphatidylinositol 3-Kinase Complexes with Mammalian Atg14 and UVRAG
Itakura, E., Kishi, C., Inoue, K., & Mizushima, N. (2008) · Molecular Biology of the Cell · doi:10.1091/mbc.e08-01-0080 · Cited by 1,176
Bif-1 interacts with Beclin 1 through UVRAG and regulates autophagy and tumorigenesis
Takahashi, Y., Coppola, D., Matsushita, N., Cualing, H. D., Sun, M., Sato, Y., Liang, C., Jung, J. U., Cheng, J. Q., Mul, J. J., et al. (2007) · Nature Cell Biology · doi:10.1038/ncb1634 · Cited by 964
Cited by
Sorted by citations
Alzheimer Disease: An Update on Pathobiology and Treatment Strategies
Long, J. M., & Holtzman, D. M. (2019) · Cell · doi:10.1016/j.cell.2019.09.001 · Cited by 3,204
A review on Alzheimer's disease pathophysiology and its management: an update
Kumar, A., Singh, A., & Ekavali (2015) · Pharmacological Reports · doi:10.1016/j.pharep.2014.09.004 · Cited by 1,578
Tau pathology and neurodegeneration
Spillantini, M. G., & Goedert, M. (2013) · The Lancet Neurology · doi:10.1016/s1474-4422(13)70090-5 · Cited by 1,133
Autophagy and Neurodegeneration: Pathogenic Mechanisms and Therapeutic Opportunities
Menzies, F. M., Fleming, A., Caricasole, A., Bento, C. F., Andrews, S. P., Ashkenazi, A., Füllgrabe, J., Jackson, A., Jimenez Sanchez, M., Karabiyik, C., et al. (2017) · Neuron · doi:10.1016/j.neuron.2017.01.022 · Cited by 1,134
Roles of tau protein in health and disease
Guo, T., Noble, W., & Hanger, D. P. (2017) · Acta Neuropathologica · doi:10.1007/s00401-017-1707-9 · Cited by 1,003
Metadata
- Authors
- Congdon, E. E., Wu, J. W., Myeku, N., Figueroa, Y. H., Herman, M., Marinec, P. S., Gestwicki, J. E., Dickey, C. A., Yu, W. H., & Duff, K. E.
- Affiliations
- New York State Psychiatric Institute (US)
- University of Michigan (US)
- University of South Florida (US)
- Corresponding author
- Duff, Karen E.
- ORCID
- Venue
- Autophagy
- Publisher
- Informa UK Limited
- Published
- 2012-04
- Volume
- 8
- Issue
- 4
- Pages
- 609-622
- ISSN
- 1554-8627 (ISSN-L)
- 1554-8635
- PMC
- PMC3405840
- OpenAlex
- W2090455820
- Cited by
- 297
- References
- 49
- Citations by year
- 2026: 9 · 2025: 9 · 2024: 16 · 2023: 10 · 2022: 21 · 2021: 29 · 2020: 37 · 2019: 14 · 2018: 16 · 2017: 23 · 2016: 27 · 2015: 26 · 2014: 25 · 2013: 23 · 2012: 10
- FWCI
- 18.23
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Autophagy (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- American Health Assistance Foundation
- Alzheimer's Drug Discovery Foundation
- National Institutes of Health
- National Institute on Aging (R00AG031291)
- National Institute of Neurological Disorders and Stroke (R01NS074593, NS074593, R01NS073899)
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Alzheimer's disease research and treatments
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Autophagy in Disease and Therapy
- Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
- Keywords
- methylene blue, tauopathy, tau aggregation, neurofibrillary tangles, frontotemporal dementia, Alzheimer's disease, Parkinson's disease, LC3-II, cathepsin D, Beclin-1, p62, neurodegenerative disease treatment, organotypic brain slice culture
- MeSH terms
- Animals, Autophagy, Brain, Cells, Cultured, Cricetinae, Humans, Lysosomes, Methylene Blue, Mice, Transgenic, Microtubule-Associated Proteins, Models, Biological, Neurons, Phosphorylation, Vacuoles, Biomarkers, CHO Cells, tau Proteins, Protein Transport, Tauopathies, Mice, Gene Knockdown Techniques
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
