ArticleFrontiers in cellular neuroscience2014
A selective histone deacetylase-6 inhibitor improves BDNF trafficking in hippocampal neurons from Mecp2 knockout mice: implications for Rett syndrome.
Article in Frontiers in cellular neuroscience, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 papers.
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29 citing papers in PubMed, 61 citations in OpenAlex.
- Traffic Jams in the Brain: How Kinesin Dysfunction Shapes Neurodevelopmental Disorders.Current issues in molecular biology · 2026Review
- Epigenetic Control of Stress-Induced Depression: Emerging Roles of HDAC3 and HDAC6.International journal of molecular sciences · 2026Review
- Single-Nucleus RNA Sequencing of HDAC6 Inhibition in Resolving Doxorubicin-Induced Cognitive Impairment.Molecular neurobiology · 2025Article
- Mutation of MeCP2 at T158M Leads to Distinct Molecular and Phenotypic Abnormalities in Male and Female Mice.Cells · 2025Article
- A Novel Histone Deacetylase 6 Inhibitor, 4-FHA, Improves Scopolamine-Induced Cognitive and Memory Impairment in Mice.Biomolecules & therapeutics · 2025Article
- A small-molecule TrkB ligand improves dendritic spine phenotypes and atypical behaviors in female Rett syndrome mice.Disease models & mechanisms · 2024Article
- Discovery of Benzylpiperazine Derivatives as CNS-Penetrant and Selective Histone Deacetylase 6 Inhibitors.ACS medicinal chemistry letters · 2022Article
- Histone deacetylase 6 inhibition restores leptin sensitivity and reduces obesity.Nature metabolism · 2022Article
- The role of altered protein acetylation in neurodegenerative disease.Frontiers in aging neuroscience · 2022Review
- Article
- Tubulin post-translational modifications control neuronal development and functions.Developmental neurobiology · 2021Review
- HDAC6 in Diseases of Cognition and of Neurons.Cells · 2020Review
- Drug Studies on Rett Syndrome: From Bench to Bedside.Journal of autism and developmental disorders · 2020Review
- MECP2 mutations affect ciliogenesis: a novel perspective for Rett syndrome and related disorders.EMBO molecular medicine · 2020Article
- Structural and in Vivo Characterization of Tubastatin A, a Widely Used Histone Deacetylase 6 Inhibitor.ACS medicinal chemistry letters · 2020Article
- Huntingtin phosphorylation governs BDNF homeostasis and improves the phenotype of Mecp2 knockout mice.EMBO molecular medicine · 2020Article
- A patent review of histone deacetylase 6 inhibitors in neurodegenerative diseases (2014-2019).Expert opinion on therapeutic patents · 2020Review
- Brain Penetrable Histone Deacetylase 6 Inhibitor SW-100 Ameliorates Memory and Learning Impairments in a Mouse Model of Fragile X Syndrome.ACS chemical neuroscience · 2019Article
- HDAC6 Brain Mapping with [ACS central science · 2017Article
- Lysine Acetylation and Deacetylation in Brain Development and Neuropathies.Genomics, proteomics & bioinformatics · 2017Review
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Authors and funding
3 authors at 2 institutions in 1 country.
Funding
Abstract
Rett syndrome (RTT) is a neurodevelopmental disorder caused by loss-of-function mutations in the transcriptional modulator methyl-CpG-binding protein 2 (MECP2). One of the most prominent gene targets of MeCP2 is brain-derived neurotrophic factor (Bdnf), a potent modulator of activity-dependent synaptic development, function and plasticity. Dysfunctional BDNF signaling has been demonstrated in several pathophysiological mechanisms of RTT disease progression. To evaluate whether the dynamics of BDNF trafficking is affected by Mecp2 deletion, we analyzed movements of BDNF tagged with yellow fluorescent protein (YFP) in cultured hippocampal neurons by time-lapse fluorescence imaging. We found that both anterograde and retrograde vesicular trafficking of BDNF-YFP are significantly impaired in Mecp2 knockout hippocampal neurons. Selective inhibitors of histone deacetylase 6 (HDAC6) show neuroprotective effects in neurodegenerative diseases and stimulate microtubule-dependent vesicular trafficking of BDNF-containing dense core vesicles. Here, we show that the selective HDAC6 inhibitor Tubastatin-A increased the velocity of BDNF-YFP vesicles in Mecp2 knockout neurons in both directions by increasing α-tubulin acetylation. Tubastatin-A also restored activity-dependent BDNF release from Mecp2 knockout neurons to levels comparable to those shown by wildtype neurons. These findings demonstrate that a selective HDAC6 inhibitor is a potential pharmacological strategy to reverse cellular and synaptic impairments in RTT resulting from impaired BDNF signaling.
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