Department of Spine Surgery, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou 510080, China.
Department of Orthopedics and Traumatology, Zhujiang Hospital, Southern Medical University, Guangzhou 510280, China.
Acta Biochim Biophys Sin (Shanghai). 2023 Oct 25;55(10):1571-1581. doi: 10.3724/abbs.2023138.
Individuals with spinal cord injury (SCI) suffer from permanent disabilities such as severe motor, sensory and autonomic dysfunction. Neural stem cell transplantation has proven to be a potential strategy to promote regeneration of the spinal cord, since NSCs can produce neurotrophic growth factors and differentiate into mature neurons to reconstruct the injured site. However, it is necessary to optimize the differentiation of NSCs before transplantation to achieve a better regenerative outcome. Inhibition of Notch signaling leads to a transition from NSCs to neurons, while the underlying mechanism remains inadequately understood. Our results demonstrate that overexpression of fucosyltransferase 9 (Fut9), which is upregulated by Wnt4, promotes neuronal differentiation by suppressing the activation of Notch signaling through disruption of furin-like enzyme activity during S1 cleavage. In an study, Fut9-modified NSCs efficiently differentiates into neurons to promote functional and histological recovery after SCI. Our research provides insight into the mechanisms of Notch signaling and a potential treatment strategy for SCI.
脊髓损伤（SCI）患者会遭受严重的运动、感觉和自主功能障碍等永久性残疾。神经干细胞（NSC）移植已被证明是一种促进脊髓再生的有潜力的策略，因为 NSCs 可以产生神经营养生长因子并分化为成熟神经元，从而重建损伤部位。然而，在移植前需要优化 NSCs 的分化，以实现更好的再生效果。抑制 Notch 信号会导致 NSCs 向神经元转化，但其潜在机制仍了解不足。我们的结果表明，Wnt4 上调的岩藻糖基转移酶 9（Fut9）通过在 S1 切割过程中破坏类枯草杆菌蛋白酶样酶活性来抑制 Notch 信号的激活，从而促进神经元分化。在一项研究中，Fut9 修饰的 NSCs 有效地分化为神经元，可促进 SCI 后的功能和组织学恢复。我们的研究为 Notch 信号的机制提供了新的见解，并为 SCI 的潜在治疗策略提供了新的思路。
