ArticleThe Journal of neuroscience : the official journal of the Society for Neuroscience2007
Histone deacetylase 6 inhibition compensates for the transport deficit in Huntington's disease by increasing tubulin acetylation.
Article in The Journal of neuroscience : the official journal of the Society for Neuroscience, 2007. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 396 papers.
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Who cites it
396 citing papers in PubMed, 771 citations in OpenAlex.
- Microtubule Cytoskeleton Dysfunction in Chronic Pain: Mechanisms of Transport Failure and Emerging Therapeutic Targets.International journal of molecular sciences · 2026Review
- HDAC6 inhibition alleviates mitochondrial trafficking in models of Charcot-Marie-Tooth disease type 2A.JCI insight · 2026Article
- Active transport by cytoplasmic dynein sustains dendritic MAP2 localization in developing neurons.The Journal of biological chemistry · 2026Article
- Post-Translational Modifications of Tubulin in Oocyte Maturation and Female Infertility.Cytoskeleton (Hoboken, N.J.) · 2026Review
- A next-generation HDAC6 inhibitor for amyotrophic lateral sclerosis and frontotemporal dementia.Brain : a journal of neurology · 2026Article
- Dissecting cytoskeletal crosstalk through reconstituted actin-microtubule systems.Molecular biology of the cell · 2026Review
- Emerging Roles of Tubulin Isoforms and Their Post-Translational Modifications in Microtubule-Based Transport and Cellular Functions.Biomolecules · 2026Review
- Deciphering the Neuroautophagic Interactome: Molecular Circuits Linking Selective Autophagy to Neuropathological Cascades in Neurological Disorders.International journal of biological sciences · 2026Review
- The tubulin code in acute ischemic stroke: post-translational reprogramming of the neuronal cytoskeleton and implications for phase-specific neuroprotection.Frontiers in neuroscience · 2026Review
- Modulating microtubule stability via α-tubulin acetylation partially restores Golgi fragmentation in spinal muscular atrophy.Turkish journal of biology = Turk biyoloji dergisi · 2026Article
- Tubastatin A attenuates impaired autophagic degradation and promotes myogenic program in skeletal muscle following downhill running.Journal of muscle research and cell motility · 2025Article
- Epigenetic Mechanisms Shaping Spine Regulation: Unveiling the Role of Cytoskeletal Dynamics and Localized Protein Synthesis.Molecular neurobiology · 2025Review
- Cerulenin partially corrects the disrupted developmental transcriptomic signature in Huntington's disease striatal medium spiny neurons.Stem cells (Dayton, Ohio) · 2025Article
- A Novel Histone Deacetylase 6 Inhibitor, 4-FHA, Improves Scopolamine-Induced Cognitive and Memory Impairment in Mice.Biomolecules & therapeutics · 2025Article
- How does the tubulin code facilitate directed cell migration?Biochemical Society transactions · 2025Review
- Rapid and sustained antidepressant effects of tubastatin A in a mouse model of depression.Scientific reports · 2025Article
- Tubulin Acetylation: A Critical Regulator of Microtubule Function.Results and problems in cell differentiation · 2025Review
- Pathogenic variants of TUBB8 cause oocyte spindle defects by disrupting with EB1/CAKP5 interactions and potential treatment targeting microtubule acetylation through HDAC6 inhibition.Clinical and translational medicine · 2025Article
- Histone modifications and depression: epigenetic mechanisms, therapeutic targets, and translational outlook.Frontiers in genetics · 2025Review
- Microtubule acetylation and PERK activation facilitate eribulin-induced mitochondrial calcium accumulation and cell death.Cellular and molecular life sciences : CMLS · 2024Article
336 more citing papers are in PubMed but not listed here.
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Authors and funding
7 authors at 2 institutions in 3 countries.
Funding
Abstract
A defect in microtubule (MT)-based transport contributes to the neuronal toxicity observed in Huntington's disease (HD). Histone deacetylase (HDAC) inhibitors show neuroprotective effects in this devastating neurodegenerative disorder. We report here that HDAC inhibitors, including trichostatin A (TSA), increase vesicular transport of brain-derived neurotrophic factor (BDNF) by inhibiting HDAC6, thereby increasing acetylation at lysine 40 of alpha-tubulin. MT acetylation in vitro and in cells causes the recruitment of the molecular motors dynein and kinesin-1 to MTs. In neurons, acetylation at lysine 40 of alpha-tubulin increases the flux of vesicles and the subsequent release of BDNF. We show that tubulin acetylation is reduced in HD brains and that TSA compensates for the transport- and release-defect phenotypes that are observed in disease. Our findings reveal that HDAC6 inhibition and acetylation at lysine 40 of alpha-tubulin may be therapeutic targets of interest in disorders such as HD in which intracellular transport is altered.
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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.