ArticlePloS one2018
A mathematical model of multisite phosphorylation of tau protein.
Article in PloS one, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 16 papers.
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Who cites it
16 citing papers in PubMed.
- Quantitative Systems Pharmacology Development and Application in Neuroscience.Handbook of experimental pharmacology · 2025Review
- Mathematical modelling of Alzheimer's disease biomarkers: Targeting Amyloid beta, Tau protein, Apolipoprotein E and Apoptotic pathways.American journal of translational research · 2024Review
- Network regulation meets substrate modification chemistry.Journal of the Royal Society, Interface · 2023Article
- Targeted Quantification of Protein Phosphorylation and Its Contributions towards Mathematical Modeling of Signaling Pathways.Molecules (Basel, Switzerland) · 2023Review
- Hallmarks of neurodegenerative disease: A systems pharmacology perspective.CPT: pharmacometrics & systems pharmacology · 2022Review
- Alzheimer's disease: Ablating single master site abolishes tau hyperphosphorylation.Science advances · 2022Article
- Monoclonal antibody therapy efficacy can be boosted by combinations with other treatments: Predictions using an integrated Alzheimer's Disease Platform.CPT: pharmacometrics & systems pharmacology · 2021Review
- Symmetry breaking meets multisite modification.eLife · 2021Article
- Exploring cyclic networks of multisite modification reveals origins of information processing characteristics.Scientific reports · 2020Article
- Quantitative Systems Pharmacology for Neuroscience Drug Discovery and Development: Current Status, Opportunities, and Challenges.CPT: pharmacometrics & systems pharmacology · 2020Article
- Applications of Quantitative Systems Pharmacology in Model-Informed Drug Discovery: Perspective on Impact and Opportunities.CPT: pharmacometrics & systems pharmacology · 2019Article
- Tau Pathology in Chronic Traumatic Encephalopathy and Alzheimer's Disease: Similarities and Differences.Frontiers in neurology · 2019Review
- Neuronal Circuit-Based Computer Modeling as a Phenotypic Strategy for CNS R&D.Frontiers in neuroscience · 2019Article
- All (animal) models (of neurodegeneration) are wrong. Are they also useful?The Journal of experimental medicine · 2018Article
- Article
- The small molecule DIPQUO promotes osteogenic differentiation via inhibition of glycogen synthase kinase 3-beta signaling.The Journal of biological chemistryArticle
Corrections and comments
- Erratum issued
Authors and funding
5 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Abnormal tau metabolism followed by formation of tau deposits causes a number of neurodegenerative diseases called tauopathies including Alzheimer's disease. Hyperphosphorylation of tau protein precedes tau aggregation and is a topic of interest for the development of pharmacological interventions to prevent pathology progression at early stages. The development of a mathematical model of multisite phosphorylation of tau would be helpful for searching for the targets of pharmacological interventions and candidates for biomarkers of pathology progression. In the present study, we for the first time developed a model of multisite phosphorylation of tau protein and elucidated the relative contribution of kinases to phosphorylation of distinct sites. The model describes phosphorylation of tau or PKA-prephosphorylated tau by GSK3β and CDK5 and dephosphorylation by PP2A, accurately reproducing the data for short-term kinetics of tau (de)phosphorylation. Our results suggest that kinase inhibition may more specifically prevent tau hyperphosphorylation, e.g., on PHF sites, which are key biomarkers of pathological changes in Alzheimer's disease. The main features of our model are partial phosphorylation of tau residues and merging of random and sequential mechanisms of multisite phosphorylation within the framework of the probability-based approach assuming independent phosphorylation events.
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