• Qingqing Wang, Hanxiao Cai, Zhenxin Hu, Yanqing Wu, Xin Guo, Jiawei Li, Haoli Wang, Yani Liu, Yanlong Liu, Ling Xie, Ke Xu, Huazi Xu, Huacheng He, Hongyu Zhang, and Jian Xiao.
• 1 Department of Orthopedics, Second Affiliated Hospital and Yuying Children's Hospital, School of Pharmaceutical Science, Wenzhou Medical University, Wenzhou, China.
• J. Neurotrauma. 2019 Jun 15; 36 (12): 1949-1964.

AbstractAxon retraction greatly limits functional recovery after spinal cord injury (SCI) and neuron polarization, which affects processes including axon formation and development, is a promising target for promoting axon regeneration. Increasing microtubule stability has been demonstrated to improve intrinsic axon regeneration processes and is critically related to endoplasmic reticulum (ER)-mitochondria interactions. We used real-time polymerase chain reaction, Western blotting, and immunofluorescence to screen a variety of natural compounds, and found that Loureirin B (LrB) effectively promoted neuron polarization and axon regeneration in vitro and in vivo. LrB significantly inhibited ER stress and thereby promoted mitochondrial functions by regulating mitochondrial fusion. Further, LrB reactivated the Akt/GSK-3β pathway, which plays critical roles in cell survival and microtubule stabilization. Taken together, our results suggest that the effects of LrB on neuron regeneration involve the inhibition of ER stress-induced mitochondrial dysfunction and activation of the Akt/GSK-3β pathway, which further promotes microtubule stabilization. LrB may therefore be a promising candidate for facilitating recovery following SCI.

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