ArticleNeuropharmacology2016
Aβ-mediated spine changes in the hippocampus are microtubule-dependent and can be reversed by a subnanomolar concentration of the microtubule-stabilizing agent epothilone D.
Article in Neuropharmacology, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 papers.
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Who cites it
31 citing papers in PubMed, 50 citations in OpenAlex.
- Endophytic Aspergillus glaucus as a novel epothilone B producer: Antiproliferative activity and in silico analysis.Applied microbiology and biotechnology · 2026Article
- Neurotransmitter Systems in Alzheimer's Disease.Current issues in molecular biology · 2026Review
- Amyloid Beta Oligomers as Early Triggers of Neuronal Cytoskeleton Dysfunction in Alzheimer's Disease.Pathophysiology : the official journal of the International Society for Pathophysiology · 2026Review
- AI-Powered Mice Behavior Tracking and Its Application for Neuronal Manifold Analysis Based on Hippocampal Ensemble Activity in an Alzheimer's Disease Mice Model.International journal of molecular sciences · 2025Article
- A Positive Allosteric Modulator of the SERCA Pump Rescues Hippocampal Neuronal Circuits Dysfunction and Cognitive Defects in a Mouse Model of Alzheimer's Disease.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2025Article
- Epothilone B from Aspergillus fumigatus with a strong antiproliferative and anti-tubulin polymerizing activities; apoptosis, and cell cycle analyses.BMC microbiology · 2025Article
- Tubulin and GTP Are Crucial Elements for Postsynaptic Density Construction and Aggregation.Journal of neurochemistry · 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
- Bioprocessing of Epothilone B from Aspergillus fumigatus under solid state fermentation: Antiproliferative activity, tubulin polymerization and cell cycle analysis.BMC microbiology · 2024Article
- IncreasediScience · 2022Article
- Super-resolution imaging and quantitative analysis of microtubule arrays in model neurons show that epothilone D increases the density but decreases the length and straightness of microtubules in axon-like processes.Brain research bulletin · 2022Article
- Review
- Upregulation of Apol8 by Epothilone D facilitates the neuronal relay of transplanted NSCs in spinal cord injury.Stem cell research & therapy · 2021Article
- Prion protein oligomers cause neuronal cytoskeletal damage in rapidly progressive Alzheimer's disease.Molecular neurodegeneration · 2021Article
- The Implication of STEP in Synaptic Plasticity and Cognitive Impairments in Alzheimer's Disease and Other Neurological Disorders.Frontiers in cell and developmental biology · 2021Review
- Enhancing microtubule stabilization rescues cognitive deficits and ameliorates pathological phenotype in an amyloidogenic Alzheimer's disease model.Scientific reports · 2020Article
- Early Effects of Aβ Oligomers on Dendritic Spine Dynamics and Arborization in Hippocampal Neurons.Frontiers in synaptic neuroscience · 2020Article
- Early-Occurring Dendritic Spines Alterations in Mouse Models of Alzheimer's Disease Inform on Primary Causes of Neurodegeneration.Frontiers in synaptic neuroscience · 2020Review
- Article
- Chronic Presence of Oligomeric Aβ Differentially Modulates Spine Parameters in the Hippocampus and Cortex of Mice With Low APP Transgene Expression.Frontiers in synaptic neuroscience · 2020Article
Corrections and comments
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Authors and funding
10 authors at 2 institutions in 2 countries.
Funding
Abstract
Dendritic spines represent the major postsynaptic input of excitatory synapses. Loss of spines and changes in their morphology correlate with cognitive impairment in Alzheimer's disease (AD) and are thought to occur early during pathology. Therapeutic intervention at a preclinical stage of AD to modify spine changes might thus be warranted. To follow the development and to potentially interfere with spine changes over time, we established a long term ex vivo model from organotypic cultures of the hippocampus from APP transgenic and control mice. The cultures exhibit spine loss in principal hippocampal neurons, which closely resembles the changes occurring in vivo, and spine morphology progressively changes from mushroom-shaped to stubby. We demonstrate that spine changes are completely reversed within few days after blocking amyloid-β (Aβ) production with the gamma-secretase inhibitor DAPT. We show that the microtubule disrupting drug nocodazole leads to spine loss similar to Aβ expressing cultures and suppresses DAPT-mediated spine recovery in slices from APP transgenic mice. Finally, we report that epothilone D (EpoD) at a subnanomolar concentration, which slightly stabilizes microtubules in model neurons, completely reverses Aβ-induced spine loss and increases thin spine density. Taken together the data indicate that Aβ causes spine changes by microtubule destabilization and that spine recovery requires microtubule polymerization. Moreover, our results suggest that a low, subtoxic concentration of EpoD is sufficient to reduce spine loss during the preclinical stage of AD.
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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.