ArticleThe Journal of biological chemistry2011
Understanding the kinetic roles of the inducer heparin and of rod-like protofibrils during amyloid fibril formation by Tau protein.
Article in The Journal of biological chemistry, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 63 papers.
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Who cites it
63 citing papers in PubMed, 143 citations in OpenAlex.
- Local Organization of Biological Membranes Modulates Tau-Lipid Interactions and Fibril formation.JACS Au · 2026Article
- From Food Additives to Neurodegeneration: The Emerging Role of Polyphosphates in Tauopathies.ACS chemical neuroscience · 2026Review
- Making tau amyloid models in vitro: a crucial and underestimated challenge.FEBS letters · 2025Review
- Chemical Synthesis Reveals Pathogenic Role ofJournal of the American Chemical Society · 2025Article
- Post-Translational Modifications Control Phase Transitions of Tau.ACS central science · 2024Article
- Fluorescence-Based Monitoring of Early-Stage Aggregation of Amyloid-β, Amylin Peptide, Tau, and α-Synuclein Proteins.ACS chemical neuroscience · 2024Article
- Post-Translational Modifications Control Phase Transitions of Tau.bioRxiv : the preprint server for biology · 2024Article
- Molecular Mechanism of Tau Misfolding and Aggregation: Insights from Molecular Dynamics Simulation.Current medicinal chemistry · 2024Review
- Blocking tau transmission by biomimetic graphene nanoparticles.Journal of materials chemistry. B · 2023Article
- DJ-1 Molecular Chaperone Activity Depresses Tau Aggregation Propensity through Interaction with Monomers.Biochemistry · 2023Article
- Chemical Features of Polyanions Modulate Tau Aggregation and Conformational States.Journal of the American Chemical Society · 2023Article
- Site-Specific C-Terminal Fluorescent Labeling of Tau Protein.ACS omega · 2022Article
- Effects of Charged Polyelectrolytes on Amyloid Fibril Formation of a Tau Fragment.ACS chemical neuroscience · 2022Article
- Quantifying Oligomer Populations in Real Time during Protein Aggregation Using Single-Molecule Mass Photometry.ACS nano · 2022Article
- The Role of Extracellular Matrix in Human Neurodegenerative Diseases.International journal of molecular sciences · 2022Review
- The Role of Post-Translational Modifications on the Structure and Function of Tau Protein.Journal of molecular neuroscience : MN · 2022Review
- Article
- Unravelling the Novel Effects of Three Volatile Compounds in Preventing Fibril Formation of Disease Related Tau and α-Synuclein Proteins- Towards Identifying Candidate Aromatic Substances for Treating Neurodegenerative Diseases.Frontiers in pharmacology · 2022Article
- The Structure Biology of Tau and Clue for Aggregation Inhibitor Design.The protein journal · 2021Review
- Article
3 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
2 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The aggregation of the natively disordered protein, Tau, to form lesions called neurofibrillary tangles is a characteristic feature of several neurodegenerative tauopathies. The polyanion, heparin, is commonly used as an inducer in studies of Tau aggregation in vitro, but there is surprisingly no comprehensive model describing, quantitatively, all aspects of the heparin-induced aggregation reaction. In this study, rate constants and extents of fibril formation by the four repeat domain of Tau (Tau4RD) have been reproducibly determined over a full range of heparin and protein concentrations. The kinetic role of heparin in the nucleation-dependent fibril formation reaction is shown to be limited to participation in the initial rate-limiting steps; a single heparin molecule binds two Tau4RD molecules, forming an aggregation-competent protein dimer, which then serves as a building block for further fibril growth. Importantly, the minimal kinetic model that is proposed can quantitatively account for the characteristic bell-shaped dependence of the aggregation kinetics on the stoichiometry of protein to heparin. Very importantly, this study also identifies for the first time short and thin, rod-like protofibrils that are populated transiently, early during the time course of fibril formation. The identification of these protofibrils as bona fide off-pathway species has implications for the development of therapies for tauopathies based on driving fibril formation as a means of protecting the cell from smaller, putatively toxic aggregates.
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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.