ArticleScientific reports2015
Methylene Blue Inhibits Caspases by Oxidation of the Catalytic Cysteine.
Article in Scientific reports, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
What it found
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The trial behind it
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Who cites it
15 citing papers in PubMed, 38 citations in OpenAlex.
- Article
- Methylene blue: a controversial diagnostic acid and medication?Toxicology research · 2022Review
- Brain Protection by Methylene Blue and Its Derivative, Azur B, via Activation of the Nrf2/ARE Pathway in Cisplatin-Induced Cognitive Impairment.Pharmaceuticals (Basel, Switzerland) · 2022Article
- The Effect of Methylene Blue and Its Metabolite-Azure I-on Bioenergetic Parameters of Intact Mouse Brain Mitochondria.Biochemistry (Moscow) Supplement. Series B, Biomedical chemistry · 2022Article
- Current and Near-Future Treatment of Alzheimer's Disease.Current neuropharmacology · 2022Article
- De Novo Molecular Design of Caspase-6 Inhibitors by a GRU-Based Recurrent Neural Network Combined with a Transfer Learning Approach.Pharmaceuticals (Basel, Switzerland) · 2021Article
- Methylene Blue Inhibits Acute Hemorrhagic Conjunctivitis Virus Production and Induction of Caspase-3 Mediated Human Corneal Cell Cytopathy.Clinical ophthalmology (Auckland, N.Z.) · 2020Article
- Methylene blue inhibits Caspase-6 activity, and reverses Caspase-6-induced cognitive impairment and neuroinflammation in aged mice.Acta neuropathologica communications · 2019Article
- Identification of Allosteric Inhibitors against Active Caspase-6.Scientific reports · 2019Article
- From Mitochondrial Function to Neuroprotection-an Emerging Role for Methylene Blue.Molecular neurobiology · 2018Review
- Microtubule affinity-regulating kinases are potential druggable targets for Alzheimer's disease.Cellular and molecular life sciences : CMLS · 2017Review
- Methylene blue inhibits NLRP3, NLRC4, AIM2, and non-canonical inflammasome activation.Scientific reports · 2017Article
- A Dual Pathogenic Mechanism Links Tau Acetylation to Sporadic Tauopathy.Scientific reports · 2017Article
- Removal of silver nanoparticles by mussel-inspired FeScientific reports · 2017Article
- Tau Protein Hyperphosphorylation and Aggregation in Alzheimer's Disease and Other Tauopathies, and Possible Neuroprotective Strategies.Biomolecules · 2016Review
Corrections and comments
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Authors and funding
5 authors at 2 institutions in 1 country.
Funding
Abstract
Methylene blue, currently in phase 3 clinical trials against Alzheimer Disease, disaggregates the Tau protein of neurofibrillary tangles by oxidizing specific cysteine residues. Here, we investigated if methylene blue can inhibit caspases via the oxidation of their active site cysteine. Methylene blue, and derivatives, azure A and azure B competitively inhibited recombinant Caspase-6 (Casp6), and inhibited Casp6 activity in transfected human colon carcinoma cells and in serum-deprived primary human neuron cultures. Methylene blue also inhibited recombinant Casp1 and Casp3. Furthermore, methylene blue inhibited Casp3 activity in an acute mouse model of liver toxicity. Mass spectrometry confirmed methylene blue and azure B oxidation of the catalytic Cys163 cysteine of Casp6. Together, these results show a novel inhibitory mechanism of caspases via sulfenation of the active site cysteine. These results indicate that methylene blue or its derivatives could (1) have an additional effect against Alzheimer Disease by inhibiting brain caspase activity, (2) be used as a drug to prevent caspase activation in other conditions, and (3) predispose chronically treated individuals to cancer via the inhibition of caspases.
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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.