ArticleThe Journal of neuroscience : the official journal of the Society for Neuroscience2012
Hyperdynamic microtubules, cognitive deficits, and pathology are improved in tau transgenic mice with low doses of the microtubule-stabilizing agent BMS-241027.
Article in The Journal of neuroscience : the official journal of the Society for Neuroscience, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 92 papers, 1 of them a synthesis that pooled it.
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Who cites it
92 citing papers in PubMed, 1 synthesis or guideline pooled it, 171 citations in OpenAlex.
- 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
- Trial
- Home-administered unfocused transcranial ultrasound in subjective cognitive decline and dementia: an open-label, uncontrolled feasibility pilot study.Frontiers in aging neuroscience · 2026Article
- Tubulin acetyltransferases access and modify the microtubule luminal K40 residue through anchors in taxane-binding pockets.Nature structural & molecular biology · 2025Article
- NRN1 may Modulate Tau Phosphorylation and Neuronal Apoptosis in ADCurrent Alzheimer research · 2025Article
- Mechanical stimulation prevents impairment of axon growth and overcompensates microtubule destabilization in cellular models of Alzheimer's disease and related Tau pathologies.Frontiers in medicine · 2025Article
- A small-molecule microtubule-stabilizing agent safely reduces Aβ plaque and tau pathology in transgenic mouse models of Alzheimer's disease.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2024Article
- A microtubule stabilizer ameliorates protein pathogenesis and neurodegeneration in mouse models of repetitive traumatic brain injury.Science translational medicine · 2023Article
- Effect of Vitamin E on Transcriptomic Alterations in Alzheimer's Disease.International journal of molecular sciences · 2023Review
- FTD-associated mutations in Tau result in a combination of dominant and recessive phenotypes.Neurobiology of disease · 2022Article
- The Role of Axonal Transport in Glaucoma.International journal of molecular sciences · 2022Review
- Review
- Network activity changes in the pathophysiology of Alzheimer's disease: the role of aging and early entorhinal cortex dysfunction.Metabolic brain disease · 2022Review
- Microtubule-modulating Agents in the Fight Against Neurodegeneration: Will it ever Work?Current neuropharmacology · 2022Review
- Review
- Novel Therapeutic Approaches for Alzheimer's Disease: An Updated Review.International journal of molecular sciences · 2021Review
- A novel orally active HDAC6 inhibitor T-518 shows a therapeutic potential for Alzheimer's disease and tauopathy in mice.Scientific reports · 2021Article
- Laterality and region-specific tau phosphorylation correlate with PTSD-related behavioral traits in rats exposed to repetitive low-level blast.Acta neuropathologica communications · 2021Article
- Tau: Enabler of diverse brain disorders and target of rapidly evolving therapeutic strategies.Science (New York, N.Y.) · 2021Review
- Plectin dysfunction in neurons leads to tau accumulation on microtubules affecting neuritogenesis, organelle trafficking, pain sensitivity and memory.Neuropathology and applied neurobiology · 2021Article
32 more citing papers are in PubMed but not listed here.
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Authors and funding
25 authors at 4 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Tau is a microtubule (MT)-stabilizing protein that is altered in Alzheimer's disease (AD) and other tauopathies. It is hypothesized that the hyperphosphorylated, conformationally altered, and multimeric forms of tau lead to a disruption of MT stability; however, direct evidence is lacking in vivo. In this study, an in vivo stable isotope-mass spectrometric technique was used to measure the turnover, or dynamicity, of MTs in brains of living animals. We demonstrated an age-dependent increase in MT dynamics in two different tau transgenic mouse models, 3xTg and rTg4510. MT hyperdynamicity was dependent on tau expression, since a reduction of transgene expression with doxycycline reversed the MT changes. Treatment of rTg4510 mice with the epothilone, BMS-241027, also restored MT dynamics to baseline levels. In addition, MT stabilization with BMS-241027 had beneficial effects on Morris water maze deficits, tau pathology, and neurodegeneration. Interestingly, pathological and functional benefits of BMS-241027 were observed at doses that only partially reversed MT hyperdynamicity. Together, these data suggest that tau-mediated loss of MT stability may contribute to disease progression and that very low doses of BMS-241027 may be useful in the treatment of AD and other tauopathies.
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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.