Department of Medicine, School of Clinical Medicine, University of Cambridge, Hills Rd, Cambridge, CB2 0SP, UK.
Faculty of Medicine, Imperial College London, London, UK.
Neural Dev. 2020 Jan 9;15(1):1. doi: 10.1186/s13064-020-0138-9.
As humans, we cannot regenerate axons within the central nervous system (CNS), therefore, making any damage to it permanent. This leads to the loss of sensory and motor function below the site of injury and can be crippling to a person's health. Spontaneous recovery can occur from plastic changes, but it is minimal. The absence of regeneration is due to the inhibitory environment of the CNS as well as the inherent inability of CNS axons to form growth cones. Amongst many factors, one of the major inhibitory signals of the CNS environment is the myelin-associated Nogo pathway. Nogo-A, Nogo-B and Nogo-C (Nogo), stimulate the Nogo receptor, inhibiting neurite outgrowth by causing growth cones to collapse through activation of Rho Kinase (ROCK). Antibodies can be used to target this signalling pathway by binding to Nogo and thus promote the outgrowth of neuronal axons in the CNS. This use of anti-Nogo antibodies has been shown to upregulate CNS regeneration as well as drastically improve sensory and motor function in both rats and primates when coupled with adequate training. Here, we evaluate whether the experimental success of anti-Nogo at improving CNS regeneration can be carried over into the clinical setting to treat spinal cord injuries (SCI) and their symptoms successfully. Furthermore, we also discuss potential methods to improve the current treatment and any developmental obstacles.
作为人类，我们无法在中枢神经系统（CNS）内再生轴突，因此任何对其造成的损伤都是永久性的。这导致损伤部位以下的感觉和运动功能丧失，可能对一个人的健康造成严重影响。虽然可以通过可塑性变化来实现自发恢复，但效果非常有限。中枢神经系统缺乏再生能力是由于其抑制性环境以及中枢神经系统轴突形成生长锥的固有能力不足所致。在众多因素中，中枢神经系统环境的主要抑制信号之一是髓鞘相关的 Nogo 通路。Nogo-A、Nogo-B 和 Nogo-C（Nogo）刺激 Nogo 受体，通过激活 Rho 激酶（ROCK）导致生长锥塌陷，从而抑制神经突生长。抗体可以通过与 Nogo 结合来靶向该信号通路，从而促进中枢神经系统神经元轴突的生长。研究表明，抗 Nogo 抗体的这种用途可以上调中枢神经系统的再生，并在与适当训练相结合时，极大地改善大鼠和灵长类动物的感觉和运动功能。在这里，我们评估抗 Nogo 在改善中枢神经系统再生方面的实验成功是否可以转化为临床应用，成功治疗脊髓损伤（SCI）及其症状。此外，我们还讨论了改善当前治疗方法和任何发展障碍的潜在方法。
