ArticleNeurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics2017
Development of Improved HDAC6 Inhibitors as Pharmacological Therapy for Axonal Charcot-Marie-Tooth Disease.
Article in Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 50 papers.
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50 citing papers in PubMed, 84 citations in OpenAlex.
- Review
- Prognostic, diagnostic and therapeutic value of the cancer tubulin code.Cancer metastasis reviews · 2026Review
- Integrated virtual screening, ADMET profiling, and molecular dynamics simulations of novel natural HDAC6 inhibitors with the potential to ameliorate skeletal muscle degeneration.Scientific reports · 2026Article
- Charcot-Marie-Tooth disease and related neuropathies.Nature reviews. Disease primers · 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
- Article
- Acetylated α-Tubulin and α-Synuclein: Physiological Interplay and Contribution to α-Synuclein Oligomerization.International journal of molecular sciences · 2023Article
- HDAC6 Deficiency Has Moderate Effects on Behaviors and Parkinson's Disease Pathology in Mice.International journal of molecular sciences · 2023Article
- Review
- HDAC6 inhibition: a significant potential regulator and therapeutic option to translate into clinical practice in renal transplantation.Frontiers in immunology · 2023Review
- HDAC-6 inhibition ameliorates the early neuropathology in a mouse model of Krabbe disease.Frontiers in molecular neuroscience · 2023Article
- Axonal transport deficits in the pathogenesis of diabetic peripheral neuropathy.Frontiers in endocrinology · 2023Review
- Histone deacetylase 6 plays an important role in TGF-β-induced murine Treg cell differentiation by regulating cell proliferation.Scientific reports · 2022Article
- Target deconvolution of HDAC pharmacopoeia reveals MBLAC2 as common off-target.Nature chemical biology · 2022Article
- Curcumin and Ethanol Effects in Trembler-J Schwann Cell Culture.Biomolecules · 2022Article
- Emerging Role of HDACs in Regeneration and Ageing in the Peripheral Nervous System: Repair Schwann Cells as Pivotal Targets.International journal of molecular sciences · 2022Review
- Role of Selective Histone Deacetylase 6 Inhibitor ACY-1215 in Cancer and Other Human Diseases.Frontiers in pharmacology · 2022Review
- Biological networks and complexity in early-onset motor neuron diseases.Frontiers in neurology · 2022Article
- The role of altered protein acetylation in neurodegenerative disease.Frontiers in aging neuroscience · 2022Review
Corrections and comments
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Authors and funding
6 authors at 3 institutions in 2 countries.
Funding
Abstract
Charcot-Marie-Tooth disease (CMT) is the most common inherited peripheral neuropathy, with an estimated prevalence of 1 in 2500. The degeneration of motor and sensory nerve axons leads to motor and sensory symptoms that progress over time and have an important impact on the daily life of these patients. Currently, there is no curative treatment available. Recently, we identified histone deacetylase 6 (HDAC6), which deacetylates α-tubulin, as a potential therapeutic target in axonal CMT (CMT2). Pharmacological inhibition of the deacetylating function of HDAC6 reversed the motor and sensory deficits in a mouse model for mutant "small heat shock protein B1" (HSPB1)-induced CMT2 at the behavioral and electrophysiological level. In order to translate this potential therapeutic strategy into a clinical application, small drug-like molecules that are potent and selective HDAC6 inhibitors are essential. To screen for these, we developed a method that consisted of 3 distinct phases and that was based on the pathological findings in the mutant HSPB1-induced CMT2 mouse model. Three different inhibitors (ACY-738, ACY-775, and ACY-1215) were tested and demonstrated to be both potent and selective HDAC6 inhibitors. Moreover, these inhibitors increased the innervation of the neuromuscular junctions in the gastrocnemius muscle and improved the motor and sensory nerve conduction, confirming that HDAC6 inhibition is a potential therapeutic strategy in CMT2. Furthermore, ACY-1215 is an interesting lead molecule as it is currently tested in clinical trials for cancer. Taken together, these results may speed up the translation of pharmacological inhibition of HDAC6 into a therapy against CMT2.
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