ArticleThe Journal of biological chemistry2013
Aminothienopyridazines and methylene blue affect Tau fibrillization via cysteine oxidation.
Article in The Journal of biological chemistry, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 67 papers.
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Who cites it
67 citing papers in PubMed, 146 citations in OpenAlex.
- Covalent Modulation of Protein Misfolding and Aggregation Processes in the Context of Neurodegenerative Diseases.Archiv der Pharmazie · 2026Review
- Regulation of autophagy-mediated pathways by diet, physical activity, and sleep in Alzheimer's disease.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2026Review
- HDAC6 Inhibition Reduces Seeded Tau and α-Synuclein Pathologies in Primary Neuron Cultures and Wild-Type Mice.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2026Article
- Dual modulation of amyloid beta and tau aggregation and dissociation in Alzheimer's disease: a comprehensive review of the characteristics and therapeutic strategies.Translational neurodegeneration · 2025Review
- Cellular Uptake of Tau Aggregates Triggers Disulfide Bond Formation in Four-Repeat Tau Monomers.ACS chemical neuroscience · 2025Article
- Mechanism of Methylene Blue Inducing the Disulfide Bond Formation of Tubulin-Associated Unit Proteins.JACS Au · 2024Article
- Hyperphosphorylated Tau Inflicts Intracellular Stress Responses that Are Mitigated by Apomorphine.Molecular neurobiology · 2024Article
- Disentangling tau: One protein, many therapeutic approaches.Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2024Review
- Methylene blue accelerates liquid-to-gel transition of tau condensates impacting tau function and pathology.Nature communications · 2023Article
- Article
- Levosimendan inhibits disulfide tau oligomerization and ameliorates tau pathology in TauExperimental & molecular medicine · 2023Article
- In Vitro Amplification of Pathogenic Tau Seeds from Neurodegenerative Disease Patient Brains.Methods in molecular biology (Clifton, N.J.) · 2023Article
- Conjugates of Methylene Blue with Cycloalkaneindoles as New Multifunctional Agents for Potential Treatment of Neurodegenerative Disease.International journal of molecular sciences · 2022Article
- Anti-fibrillization effects of sulfonamide derivatives onJournal of molecular structure · 2022Article
- The Role of Post-Translational Modifications on the Structure and Function of Tau Protein.Journal of molecular neuroscience : MN · 2022Review
- Mical modulates Tau toxicity via cysteine oxidation in vivo.Acta neuropathologica communications · 2022Article
- Amyloid Cross-Seeding: Mechanism, Implication, and Inhibition.Molecules (Basel, Switzerland) · 2022Review
- Joint Computational/Cell-Based Approach for Screening Inhibitors of Tau Oligomerization: A Proof-of-Concept Study.Journal of Alzheimer's disease : JAD · 2022Article
- Solid-state NMR of paired helical filaments formed by the core tau fragment tau(297-391).Frontiers in neuroscience · 2022Article
- [Neuroprotective treatment of tauopathies].Der Nervenarzt · 2021Review
7 more citing papers are in PubMed but not listed here.
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Authors and funding
7 authors at 1 institution in 1 country.
Funding
Abstract
Alzheimer disease and several other neurodegenerative disorders are characterized by the accumulation of intraneuronal fibrils comprised of the protein Tau. Tau is normally a soluble protein that stabilizes microtubules, with splice isoforms that contain either three (3-R) or four (4-R) microtubule binding repeats. The formation of Tau fibrils is thought to result in neuronal damage, and inhibitors of Tau fibrillization may hold promise as therapeutic agents. The process of Tau fibrillization can be replicated in vitro, and a number of small molecules have been identified that inhibit Tau fibril formation. However, little is known about how these molecules affect Tau fibrillization. Here, we examined the mechanism by which the previously described aminothieno pyridazine (ATPZ) series of compounds inhibit Tau fibrillization. Active ATPZs were found to promote the oxidation of the two cysteine residues within 4-R Tau by a redox cycling mechanism, resulting in the formation of a disulfide-containing compact monomer that was refractory to fibrillization. Moreover, the ATPZs facilitated intermolecular disulfide formation between 3-R Tau monomers, leading to dimers that were capable of fibrillization. The ATPZs also caused cysteine oxidation in molecules unrelated to Tau. Interestingly, methylene blue, an inhibitor of Tau fibrillization under evaluation in Alzheimer disease clinical trials, caused a similar oxidation of cysteines in Tau and other molecules. These findings reveal that the ATPZs and methylene blue act by a mechanism that may affect their viability as potential therapeutic agents.
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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.