ArticleBiology open2014
Low dose tubulin-binding drugs rescue peroxisome trafficking deficit in patient-derived stem cells in Hereditary Spastic Paraplegia.
Article in Biology open, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers, 1 of them a synthesis that pooled it.
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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
28 citing papers in PubMed, 1 synthesis or guideline pooled it.
- Motor Evoked Potentials in Hereditary Spastic Paraplegia-A Systematic Review.Frontiers in neurology · 2019Pooled it
- Effects of Epothilone D on Social Defeat Stress-induced Changes in Microtubule-related and Endoplasmic Reticulum Stress Protein Expression.Clinical psychopharmacology and neuroscience : the official scientific journal of the Korean College of Neuropsychopharmacology · 2025Article
- Outcome Measures and Biomarkers for Clinical Trials in Hereditary Spastic Paraplegia: A Scoping Review.Genes · 2023Article
- Reduced acetylated α-tubulin inFrontiers in neuroscience · 2023Article
- The interconnection of endoplasmic reticulum and microtubule and its implication in Hereditary Spastic Paraplegia.Computational and structural biotechnology journal · 2023Review
- The Role of Spastin in Axon Biology.Frontiers in cell and developmental biology · 2022Review
- Therapeutic Strategies for MutantBrain sciences · 2021Review
- Single cell morphology distinguishes genotype and drug effect in Hereditary Spastic Paraplegia.Scientific reports · 2021Article
- Analyzing Olfactory Neuron Precursors Non-Invasively Isolated through NADH FLIM as a Potential Tool to Study Oxidative Stress in Alzheimer's Disease.International journal of molecular sciences · 2021Review
- Hereditary Spastic Paraplegia: From Genes, Cells and Networks to Novel Pathways for Drug Discovery.Brain sciences · 2021Review
- Regulation of peroxisomal trafficking and distribution.Cellular and molecular life sciences : CMLS · 2021Review
- Challenges and Controversies in the Genetic Diagnosis of Hereditary Spastic Paraplegia.Current neurology and neuroscience reports · 2021Review
- Spastin recovery in hereditary spastic paraplegia by preventing neddylation-dependent degradation.Life science alliance · 2020Article
- Microtubule Dysfunction: A Common Feature of Neurodegenerative Diseases.International journal of molecular sciences · 2020Review
- Oxidative Stress-Induced Axon Fragmentation Is a Consequence of Reduced Axonal Transport in Hereditary Spastic ParaplegiaFrontiers in neuroscience · 2020Article
- Hereditary spastic paraplegia: gain-of-function mechanisms revealed by new transgenic mouse.Human molecular genetics · 2019Article
- Update on the Genetics of Spastic Paraplegias.Current neurology and neuroscience reports · 2019Review
- Defects in Axonal Transport in Inherited Neuropathies.Journal of neuromuscular diseases · 2019Review
- Patient-Derived Stem Cell Models inBrain sciences · 2018Review
- New splicing variants of mitochondrial Rho GTPase-1 (Miro1) transport peroxisomes.The Journal of cell biology · 2018Article
Corrections and comments
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Authors and funding
7 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Hereditary Spastic Paraplegia (HSP) is a genetically heterogeneous group of disorders, diagnosed by progressive gait disturbances with muscle weakness and spasticity, for which there are no treatments targeted at the underlying pathophysiology. Mutations in spastin are a common cause of HSP. Spastin is a microtubule-severing protein whose mutation in mouse causes defective axonal transport. In human patient-derived olfactory neurosphere-derived (ONS) cells, spastin mutations lead to lower levels of acetylated α-tubulin, a marker of stabilised microtubules, and to slower speed of peroxisome trafficking. Here we screened multiple concentrations of four tubulin-binding drugs for their ability to rescue levels of acetylated α-tubulin in patient-derived ONS cells. Drug doses that restored acetylated α-tubulin to levels in control-derived ONS cells were then selected for their ability to rescue peroxisome trafficking deficits. Automated microscopic screening identified very low doses of the four drugs (0.5 nM taxol, 0.5 nM vinblastine, 2 nM epothilone D, 10 µM noscapine) that rescued acetylated α-tubulin in patient-derived ONS cells. These same doses rescued peroxisome trafficking deficits, restoring peroxisome speeds to untreated control cell levels. These results demonstrate a novel approach for drug screening based on high throughput automated microscopy for acetylated α-tubulin followed by functional validation of microtubule-based peroxisome transport. From a clinical perspective, all the drugs tested are used clinically, but at much higher doses. Importantly, epothilone D and noscapine can enter the central nervous system, making them potential candidates for future clinical trials.
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