Molecules and Cells

Korean Society for Molecular and Cellular Biology (한국분자세포생물학회)
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Therapeutic Potential of CKD-504, a Novel Selective Histone Deacetylase 6 Inhibitor, in a Zebrafish Model of Neuromuscular Junction Disorders

  • Jeong, Hui Su (Department of Health Sciences and Technology, Samsung Advanced Institute for Health Sciences & Technology, Sungkyunkwan University) ;
  • Kim, Hye Jin (Department of Health Sciences and Technology, Samsung Advanced Institute for Health Sciences & Technology, Sungkyunkwan University) ;
  • Kim, Deok-Ho (Department of Biomedical Engineering, Johns Hopkins University) ;
  • Chung, Ki Wha (Department of Biological Sciences, Kongju National University) ;
  • Choi, Byung-Ok (Department of Health Sciences and Technology, Samsung Advanced Institute for Health Sciences & Technology, Sungkyunkwan University) ;
  • Lee, Ji Eun (Department of Health Sciences and Technology, Samsung Advanced Institute for Health Sciences & Technology, Sungkyunkwan University)
  • Received : 2021.10.11
  • Accepted : 2021.12.25
  • Published : 2022.04.30
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Abstract

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.

Keywords

Acknowledgement

This work was supported by the National Research Foundation, funded by the Korean government's MSIP (2021R1A2C3004572 to J.E.L., 2021R1A6A3A13041249 to H.S.J., 2021R1A4A2001389 to K.W.C., B.O.C., and J.E.L.), and was supported by the National Institutes of Health, USA (NIH RO1 NS094388 to B.O.C. and D.H.K.).

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