期刊
STEM CELL REPORTS
卷 4, 期 4, 页码 561-568出版社
CELL PRESS
DOI: 10.1016/j.stemcr.2015.02.010
关键词
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资金
- Ministry of Health, Labour and Welfare of Japan
- Ministry of Education, Culture, Sports, Science and Technology of Japan
- Ministry of Education, Culture, Sports, Science and Technology
- Japan Society for the Promotion of Science
- Japan Science and Technology Agency (JST)
- CREST
- Ministry of Education, Culture, Sports, Science and Technology of Japan (Innovative Area Foundation of Synapse and Neurocircuit Pathology) [22110007]
- Program for Intractable Diseases Research utilizing disease-specific iPS cells of JST
- Japan Research Foundation for Clinical Pharmacology
- Mochida Memorial Foundation for Medical and Pharmaceutical Research
- NCNP [24-9]
- Grants-in-Aid for Scientific Research [22110007, 15K06921, 25461591] Funding Source: KAKEN
Spinal muscular atrophy (SMA) is a neuromuscular disorder caused by mutations of the survival of motor neuron 1 (SMN1) gene. In the pathogenesis of SMA, pathological changes of the neuromuscular junction (NMJ) precede the motor neuronal loss. Therefore, it is critical to evaluate the NMJ formed by SMA patients' motor neurons (MNs), and to identify drugs that can restore the normal condition. We generated NMJ-like structures using MNs derived from SMA patient-specific induced pluripotent stem cells (iPSCs), and found that the clustering of the acetylcholine receptor (AChR) is significantly impaired. Valproic acid and antisense oligonucleotide treatment ameliorated the AChR clustering defects, leading to an increase in the level of full-length SMN transcripts. Thus, the current in vitro model of AChR clustering using SMA patient-derived iPSCs is useful to dissect the pathophysiological mechanisms underlying the development of SMA, and to evaluate the efficacy of new therapeutic approaches.
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