PDF(Pubmed)
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.
摘要：
神经肌肉接头（NMJ），它是从运动神经元到肌肉细胞的信号传递的突触，已成为重要区域，因为它与几种周围神经病变有关。特别是,GARS中影响NMJ形成的突变导致Charcot-Marie-Tooth病和远端遗传性运动神经病。这些疾病主要被认为是由神经元轴突异常引起的；然而，目前没有可用的治疗方法。因此,为了确定NMJ是否可以靶向治疗神经退行性疾病，我们调查了HDAC6抑制剂的NMJ恢复效果，已用于治疗多种周围神经病变。在本研究中,我们证明，HDAC6抑制足以通过恢复斑马鱼疾病模型中观察到的NMJ损伤来增强运动。我们发现CKD-504，一种新型的HDAC6抑制剂，能有效修复NMJ的缺陷,提示通过NMJ靶向治疗神经退行性疾病是可能的。
