Synthetic Small Molecules that Induce Neurogenesis in Skeletal Muscle

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.