Synthetic small molecules that induce neurogenesis in skeletal muscle.
Synthetic small molecules that induce neurogenesis in skeletal muscle.
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DOI：
10.1021/ja072817z
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发表时间：
2007-07
影响因子：
15
通讯作者：
D. Williams;Myung-ryul Lee;You Song;Sung-Kyun Ko;Gun-Hee Kim;I. Shin
中科院分区：
文献类型：
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作者：
D. Williams;Myung-ryul Lee;You Song;Sung-Kyun Ko;Gun-Hee Kim;I. Shin
神经元不能有效再生，损伤会导致神经退行性疾病。这些疾病可以通过神经干细胞移植来治疗。然而，伦理和技术问题限制了使用神经干细胞的细胞治疗。一种更方便、更有吸引力的方法是使用具有从容易获得的细胞或组织中诱导神经发生能力的小分子。这种小分子有可能严格控制细胞分化的时间和速度。在这里，我们描述了通过筛选C2C12成肌细胞的咪唑文库鉴定出的第一个这样的分子neurodazine的发现。进一步的分析表明，neurodazine促进了C2C12细胞中神经元特异性标记物的表达。此外，神经dazines与微管不稳定剂联合使用可使分化的未成熟肌管和成熟骨骼肌发生神经源性转化。
Neurons are not regenerated effectively, and their injury causes neurodegenerative diseases. These diseases may be treated by the transplantation of neural stem cells. However, ethical and technical issues restrict cell therapies using neural stem cells. A more convenient and attractive approach is the use of small molecules with the capacity to induce neurogenesis from easily available cells or tissues. Such small molecules have the potential to allow tight controls over the timing and speed of cell differentiation. Herein, we describe the discovery of the first such molecule, neurodazine, identified by screening an imidazole library with C2C12 myoblasts. Further analyses show that neurodazine promotes the expression of neuron-specific markers in treated C2C12 cells. In addition, the use of neurodazines in conjunction with a microtubule-destabilizing agent allows neurogenic conversion of both differentiated immature myotubes and mature skeletal muscle.