ArticleNature communications2018
Aberrant GlyRS-HDAC6 interaction linked to axonal transport deficits in Charcot-Marie-Tooth neuropathy.
Article in Nature communications, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 71 papers.
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Who cites it
71 citing papers in PubMed, 114 citations in OpenAlex.
- 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
- Locally synthesized glycyl aminoacyl-tRNA synthetase is important for local translation in neurons.Life science alliance · 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
- Transfer RNA and small molecule therapeutics for aminoacyl-tRNA synthetase diseases.The FEBS journal · 2025Review
- Inhibition of histone deacetylase 6 activity mitigates neurological impairment and post-hemorrhagic hydrocephalus after intraventricular hemorrhage by modulating pyroptosis and autophagy pathways.Fluids and barriers of the CNS · 2025Article
- Glycyl-tRNA sequestration is a unifying mechanism underlying GARS1-associated peripheral neuropathy.Nucleic acids research · 2025Article
- Aminoacyl-tRNA synthetase defects in neurological diseases.IUBMB life · 2025Review
- Citric Acid: A Nexus Between Cellular Mechanisms and Biomaterial Innovations.Advanced materials (Deerfield Beach, Fla.) · 2024Review
- Boosting BDNF in muscle rescues impaired axonal transport in a mouse model of DI-CMTC peripheral neuropathy.Neurobiology of disease · 2024Article
- Lack of effect from genetic deletion of Hdac6 in a humanized mouse model of CMT2D.Journal of the peripheral nervous system : JPNS · 2024Article
- A missense mutation in human INSC causes peripheral neuropathy.EMBO molecular medicine · 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
- Docking protein 6 (DOK6) selectively docks the neurotrophic signaling transduction to restrain peripheral neuropathy.Signal transduction and targeted therapy · 2024Article
- Uncovering the mystery of genetic heterogeneity in inherited peripheral neuropathies.Life medicine · 2023Article
- High expression of VARS promotes the growth of multiple myeloma cells by causing imbalance in valine metabolism.Zhong nan da xue xue bao. Yi xue ban = Journal of Central South University. Medical sciences · 2023Article
- A humanized yeast model reveals dominant-negative properties of neuropathy-associated alanyl-tRNA synthetase mutations.Human molecular genetics · 2023Article
11 more citing papers are in PubMed but not listed here.
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Authors and funding
15 authors at 5 institutions in 1 country.
Funding
Abstract
Dominant mutations in glycyl-tRNA synthetase (GlyRS) cause a subtype of Charcot-Marie-Tooth neuropathy (CMT2D). Although previous studies have shown that GlyRS mutants aberrantly interact with Nrp1, giving insight into the disease's specific effects on motor neurons, these cannot explain length-dependent axonal degeneration. Here, we report that GlyRS mutants interact aberrantly with HDAC6 and stimulate its deacetylase activity on α-tubulin. A decrease in α-tubulin acetylation and deficits in axonal transport are observed in mice peripheral nerves prior to disease onset. An HDAC6 inhibitor used to restore α-tubulin acetylation rescues axonal transport deficits and improves motor functions of CMT2D mice. These results link the aberrant GlyRS-HDAC6 interaction to CMT2D pathology and suggest HDAC6 as an effective therapeutic target. Moreover, the HDAC6 interaction differs from Nrp1 interaction among GlyRS mutants and correlates with divergent clinical presentations, indicating the existence of multiple and different mechanisms in CMT2D.
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