ArticleProceedings of the National Academy of Sciences of the United States of America2003
Differential regulation of microtubule dynamics by three- and four-repeat tau: implications for the onset of neurodegenerative disease.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2003. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 143 papers, 1 of them a synthesis that pooled it.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
143 citing papers in PubMed, 1 synthesis or guideline pooled it.
- Similarities and Differences in the Pattern of Tau Hyperphosphorylation in Physiological and Pathological Conditions: Impacts on the Elaboration of Therapies to Prevent Tau Pathology.Frontiers in neurology · 2020Pooled it
- Article
- Patient-derived tau-seeded human neuronal chimeras recapitulate mature Alzheimer's tau pathology and uncover human-specific neuronal vulnerability.bioRxiv : the preprint server for biology · 2026Article
- Dysregulation of the Tau-Microtubule-End-Binding Protein Axis in Alzheimer's Disease and Related Tauopathies.International journal of molecular sciences · 2026Review
- A coherent structural picture of the interaction of Tau with tubulin provides a link to its aggregation.The Journal of biological chemistry · 2026Review
- Investigating the Causal Links between the Aging Process and Alzheimer's Disease Pathogenesis.International journal of stem cells · 2026Review
- Autophagy Activators Normalize Aberrant Tau Proteostasis and Rescue Synapses in Human Familial Alzheimer's Disease iPSC-Derived Cortical Organoids.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- The power and limits of predicting inter-protein exon-exon interactions using protein 3D structures.Bioinformatics advances · 2026Article
- Mining Alzheimer's Interactomes, Macromolecular Complexes and Pathways for Drug Discovery.Proteomics · 2025Review
- A high-throughput drug screening assay for anti-tau aggregation using split GFP and flow cytometry.Scientific reports · 2025Article
- Cell autonomous microglia defects in a stem cell model of frontotemporal dementia tau.Molecular psychiatry · 2025Article
- Herpes simplex virus-1 infection alters microtubule-associated protein Tau splicing and promotes Tau pathology in neural models of Alzheimer's disease.Brain pathology (Zurich, Switzerland) · 2025Article
- Multifactorial etiology of progressive supranuclear palsy (PSP): the genetic component.Acta neuropathologica · 2025Review
- Differences in the soluble and insoluble proteome between primary tauopathies.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2025Article
- Diverse influences on tau aggregation and implications for disease progression.Genes & development · 2025Review
- Tau-targeting nanoparticles for treatment of Alzheimer's disease.Exploration (Beijing, China) · 2025Review
- Development of MAPT S305 mutation human iPSC lines exhibiting elevated 4R tau expression and functional alterations in neurons and astrocytes.Cell reports · 2024Article
- Tau Isoform-Regulated Schwann Cell Proliferation and Migration Improve Peripheral Nerve Regeneration After Injury.International journal of molecular sciences · 2024Article
- Cellular and pathological functions of tau.Nature reviews. Molecular cell biology · 2024Review
- The structure of a Tau fragment bound to tubulin prompts new hypotheses on Tau mechanism and oligomerization.PNAS nexus · 2024Article
83 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
5 authors.
Funding
Abstract
The microtubule (MT)-associated protein tau is important in neuronal development and in Alzheimer's and other neurodegenerative diseases. Genetic analyses have established a cause-and-effect relationship between tau dysfunction/misregulation and neuronal cell death and dementia in frontotemporal dementia and parkinsonism associated with chromosome 17; several mutations causing this dementia lead to increased ratios of four-repeat (4R) to three-repeat (3R) wild-type tau, and an attractive hypothesis is that the abnormally high ratio of 4R to 3R tau might lead to neuronal cell death by altering normal tau functions in adult neurons. Thus, we tested whether 3R and 4R tau might differentially modulate the dynamic instability of MTs in vitro using video microscopy. Although both isoforms promoted MT polymerization and decreased the tubulin critical subunit concentration to approximately similar extents, 4R tau stabilized MTs significantly more strongly that 3R tau. For example, 4R tau suppressed the shortening rate, whereas 3R tau had little or no detectable effect. Similarly, 3R tau had no effect on the length shortened during a shortening event, whereas 4R tau strongly reduced this parameter. Further, when MTs were diluted into buffer containing 4R tau, the MTs were stabilized and shortened slowly. In contrast, when diluted into 3R tau, the MTs were unstable and shortened rapidly. Thus, 4R tau stabilizes MTs differently and significantly more strongly than 3R tau. We suggest a "dosage effect" or haploinsufficiency model in which both tau alleles must be active and properly regulated to produce appropriate amounts of each tau isoform to maintain MT dynamics within a tolerable window of activity.
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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.