ArticleThe Journal of neuroscience : the official journal of the Society for Neuroscience2012
The microtubule-stabilizing agent, epothilone D, reduces axonal dysfunction, neurotoxicity, cognitive deficits, and Alzheimer-like pathology in an interventional study with aged tau transgenic mice.
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 213 papers, 1 of them a synthesis that pooled it.
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Who cites it
213 citing papers in PubMed, 1 synthesis or guideline pooled it, 399 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
- Post-traumatic stress disorder: pathogenesis, epidemiological characteristics, animal models, and potential therapeutic strategies.Military Medical Research · 2026Review
- When the Cytoskeleton Fails: Primary Structural Defects Underlying Disorders with Neurological Involvement.International journal of molecular sciences · 2026Review
- Tau physiology and pathology: impacts on cellular structures and neurodegenerative diseases.Inflammopharmacology · 2026Review
- FKBP51 inhibition by SAFit2 modulates tau pathology and cognitive deficits in PS19 mice.Alzheimer's research & therapy · 2026Article
- Biophysical assessment of the molecular mechanisms of Tau aggregation and its role in Alzheimer's disease.Protein science : a publication of the Protein Society · 2026Review
- Dominant α-tubulin mutations rescue tauopathy neurodegenerative phenotypes inbioRxiv : the preprint server for biology · 2026Article
- An Integrated QSAR-MD-DCCM Pipeline: A Predictive Computational Platform for the Rational Design and Dynamic Functional Validation of Dual-Target Directed Ligands.Pharmaceuticals (Basel, Switzerland) · 2026Article
- 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
- Transient entanglement in minimal open XXZ spin chains: a toy-model analogy for microtubule-inspired quantum biology.Frontiers in psychiatry · 2026Article
- Home-administered unfocused transcranial ultrasound in subjective cognitive decline and dementia: an open-label, uncontrolled feasibility pilot study.Frontiers in aging neuroscience · 2026Article
- Cytoskeleton-mediated autophagy regulation in neuroimmune contexts: molecular mechanisms and functional perspectives.Frontiers in immunology · 2026Review
- The Central Role of Actin in Creutzfeldt-Jakob Disease: Unlocking Therapeutic Pathways.Molecular neurobiology · 2025Review
- APOE deficiency inhibits amyloid-facilitated (A) tau pathology (T) and neurodegeneration (N), halting progressive ATN pathology in a preclinical model.Molecular psychiatry · 2025Article
- Circadian timing and entrainment properties of the SCN pacemaker in the PS19 mouse model of tau pathology.Experimental neurology · 2025Article
- Imaging microtubule dynamics: A new frontier in biomarker development for neurodegenerative diseases.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2025Review
- Microtubule-Targeting Agents: Advances in Tubulin Binding and Small Molecule Therapy for Gliomas and Neurodegenerative Diseases.International journal of molecular sciences · 2025Review
- Cytoskeletal Proteins and Alzheimer's Disease Pathogenesis: Focusing on the Interplay with Tau Pathology.Biomolecules · 2025Review
- Alzheimer's Disease and Frontotemporal Dementia: A Review of Pathophysiology and Therapeutic Approaches.Journal of neuroscience research · 2025Review
- Article
153 more citing papers are in PubMed but not listed here.
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Authors and funding
12 authors at 2 institutions in 1 country.
Funding
Abstract
Neurodegenerative tauopathies, such as Alzheimer's disease (AD), are characterized by insoluble deposits of hyperphosphorylated tau protein within brain neurons. Increased phosphorylation and decreased solubility has been proposed to diminish normal tau stabilization of microtubules (MTs), thereby leading to neuronal dysfunction. Earlier studies have provided evidence that small molecule MT-stabilizing drugs that are used in the treatment of cancer may have utility in the treatment of tauopathies. However, it has not been established whether treatment with a small molecule MT-stabilizing compound will provide benefit in a transgenic model with pre-existing tau pathology, as would be seen in human patients with clinical symptoms. Accordingly, we describe here an interventional study of the brain-penetrant MT-stabilizing agent, epothilone D (EpoD), in aged PS19 mice with existing tau pathology and related behavioral deficits. EpoD treatment reduced axonal dystrophy and increased axonal MT density in the aged PS19 mice, which led to improved fast axonal transport and cognitive performance. Moreover, the EpoD-treated PS19 mice had less forebrain tau pathology and increased hippocampal neuronal integrity, with no dose-limiting side effects. These data reveal that brain-penetrant MT-stabilizing drugs hold promise for the treatment of AD and related tauopathies, and that EpoD could be a candidate for clinical testing.
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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.