Therapeutic Potential of CKD-504, a Novel Selective Histone Deacetylase 6 Inhibitor, in a Zebrafish Model of Neuromuscular Junction Disorders
- Jeong, H.S., Kim, H.J., Kim, D.H., Chung, K.W., Choi, B.O., Lee, J.E.
- Molecules and cells 45(4): 231-242 (Journal)
- Registered Authors
- Jeong, Hui Su, Lee, Ji Eun
- CKD-504, GARS, HDAC6 inhibitor, Neuromuscular Junction, Zebrafish
- MeSH Terms
- Charcot-Marie-Tooth Disease*/drug therapy
- Charcot-Marie-Tooth Disease*/genetics
- Histone Deacetylase 6
- Neuromuscular Junction Diseases*
- Renal Insufficiency, Chronic*
- 35356895 Full text @ Mol. Cells
Jeong, H.S., Kim, H.J., Kim, D.H., Chung, K.W., Choi, B.O., Lee, J.E. (2022) Therapeutic Potential of CKD-504, a Novel Selective Histone Deacetylase 6 Inhibitor, in a Zebrafish Model of Neuromuscular Junction Disorders. Molecules and cells. 45(4):231-242.
The neuromuscular junction (NMJ), which is a synapse for signal transmission from motor neurons to muscle cells, has emerged as an important region because of its association with several peripheral neuropathies. In particular, mutations in GARS that affect the formation of NMJ result in Charcot-Marie-Tooth disease and distal hereditary motor neuropathy. These disorders are mainly considered to be caused by neuronal axon abnormalities; however, no treatment is currently available. Therefore, in order to determine whether the NMJ could be targeted to treat neurodegenerative disorders, we investigated the NMJ recovery effect of HDAC6 inhibitors, which have been used in the treatment of several peripheral neuropathies. In the present study, we demonstrated that HDAC6 inhibition was sufficient to enhance movement by restoring NMJ impairments observed in a zebrafish disease model. We found that CKD-504, a novel HDAC6 inhibitor, was effective in repairing NMJ defects, suggesting that treatment of neurodegenerative diseases via NMJ targeting is possible.
Genes / Markers
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Engineered Foreign Genes