ArticleBrain : a journal of neurology2018
HDAC6 is a therapeutic target in mutant GARS-induced Charcot-Marie-Tooth disease.
Article in Brain : a journal of neurology, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 75 papers.
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Who cites it
75 citing papers in PubMed, 120 citations in OpenAlex.
- An integrated machine learning and chemical space network approach for the design of potent epigenetic HDAC6 inhibitors for targeting neurological disorders.Molecular diversity · 2026Article
- HDAC6 inhibition alleviates mitochondrial trafficking in models of Charcot-Marie-Tooth disease type 2A.JCI insight · 2026Article
- The neuropathy-causingbioRxiv : the preprint server for biology · 2026Article
- Junctions in Jeopardy: the neuromuscular junction is a selective pathological target in Charcot-Marie-Tooth disease.Mammalian genome : official journal of the International Mammalian Genome Society · 2026Review
- Single-Nucleus RNA Sequencing of HDAC6 Inhibition in Resolving Doxorubicin-Induced Cognitive Impairment.Molecular neurobiology · 2025Article
- ITF6475, a New Histone Deacetylase 6 Inhibitor, Prevents Painful Neuropathy Induced by Paclitaxel.Toxics · 2025Article
- Glycyl-tRNA sequestration is a unifying mechanism underlying GARS1-associated peripheral neuropathy.Nucleic acids research · 2025Article
- Insights into phenotypic variability caused by GARS1 pathogenic variants.European journal of neurology · 2024Observational
- PMP22 duplication dysregulates lipid homeostasis and plasma membrane organization in developing human Schwann cells.Brain : a journal of neurology · 2024Article
- Histone deacetylase 6 controls cardiac fibrosis and remodelling through the modulation of TGF-β1/Smad2/3 signalling in post-infarction mice.Journal of cellular and molecular medicine · 2024Article
- The various forms of hereditary motor neuron disorders and their historical descriptions.Journal of neurology · 2024Review
- A novel insight into neurological disorders through HDAC6 protein-protein interactions.Scientific reports · 2024Article
- Lack of effect from genetic deletion of Hdac6 in a humanized mouse model of CMT2D.Journal of the peripheral nervous system : JPNS · 2024Article
- Ketamine impairs growth cone and synaptogenesis in human GABAergic projection neurons via GSK-3β and HDAC6 signaling.Molecular psychiatry · 2024Article
- Boosting BDNF in muscle rescues impaired axonal transport in a mouse model of DI-CMTC peripheral neuropathy.Neurobiology of disease · 2024Article
- Molecular mechanisms and therapeutic strategies for neuromuscular diseases.Cellular and molecular life sciences : CMLS · 2024Review
- Boosting BDNF in muscle rescues impaired axonal transport in a mouse model of DI-CMTC peripheral neuropathy.bioRxiv : the preprint server for biology · 2024Article
- Inhibition of HDAC6 promotes microvascular endothelial cells to phagocytize myelin debris and reduces inflammatory response to accelerate the repair of spinal cord injury.CNS neuroscience & therapeutics · 2024Article
- CGRP promotes osteogenic differentiation by regulating macrophage M2 polarization through HDAC6/AKAP12 signaling pathway.Regenerative medicine · 2024Article
- HDAC6 inhibition regulates substrate stiffness-mediated inflammation signaling in chondrocytes.Acta biochimica et biophysica Sinica · 2023Article
15 more citing papers are in PubMed but not listed here.
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Authors and funding
15 authors at 4 institutions in 3 countries.
Funding
Abstract
Peripheral nerve axons require a well-organized axonal microtubule network for efficient transport to ensure the constant crosstalk between soma and synapse. Mutations in more than 80 different genes cause Charcot-Marie-Tooth disease, which is the most common inherited disorder affecting peripheral nerves. This genetic heterogeneity has hampered the development of therapeutics for Charcot-Marie-Tooth disease. The aim of this study was to explore whether histone deacetylase 6 (HDAC6) can serve as a therapeutic target focusing on the mutant glycyl-tRNA synthetase (GlyRS/GARS)-induced peripheral neuropathy. Peripheral nerves and dorsal root ganglia from the C201R mutant Gars mouse model showed reduced acetylated α-tubulin levels. In primary dorsal root ganglion neurons, mutant GlyRS affected neurite length and disrupted normal mitochondrial transport. We demonstrated that GlyRS co-immunoprecipitated with HDAC6 and that this interaction was blocked by tubastatin A, a selective inhibitor of the deacetylating function of HDAC6. Moreover, HDAC6 inhibition restored mitochondrial axonal transport in mutant GlyRS-expressing neurons. Systemic delivery of a specific HDAC6 inhibitor increased α-tubulin acetylation in peripheral nerves and partially restored nerve conduction and motor behaviour in mutant Gars mice. Our study demonstrates that α-tubulin deacetylation and disrupted axonal transport may represent a common pathogenic mechanism underlying Charcot-Marie-Tooth disease and it broadens the therapeutic potential of selective HDAC6 inhibition to other genetic forms of axonal Charcot-Marie-Tooth disease.
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