Department of Pharmacology and Toxicology, National Institute of Pharmaceutical Education and Research (NIPER)-Ahmedabad, Gandhinagar, Gujarat, India.
Department of Pharmacology and Toxicology, National Institute of Pharmaceutical Education and Research (NIPER)-Ahmedabad, Gandhinagar, Gujarat, India.
Neuroscience. 2023 Nov 21;533:36-52. doi: 10.1016/j.neuroscience.2023.08.034. Epub 2023 Sep 11.
Axon guidance molecules (AGM) are critical regulators of neural development and play a vital role in guiding axons to their target regions during spinal cord development. The correct wiring of neural circuits depends on these molecules' precise expression and function. Defects in axonal pathfinding, growth cone navigation, axonal branching, and synapse formation have far-reaching implications for neuronal circuit construction and function after CNS traumas, such as spinal cord injury (SCI), which affect the expression or activity of AGM. Ascending and descending paths in the spinal cord have been found to include many AGM, including Netrins, Slits, Semaphorins (Sema), Ephrins, and their receptors. In contrast to the repulsive signals like Slits and Semaphorins, which restrict axonal growth and guide axons away from unsuitable locations, Netrins are appealing guidance cues that encourage axonal growth and guidance. Defects in motor function and sensory processing can result from changes in the expression or activity of Ephrins or their receptors, which play an essential role in axonal guidance and synaptic plasticity in the spinal cord. Herein, we highlighted the expressions, functions, and mechanisms of AGM in ascending and descending spinal cord tracts, which can help us identify novel therapeutic targets to improve axonal regeneration and functional recovery after SCI.
轴突导向分子(AGM)是神经发育的关键调节因子,在脊髓发育过程中指导轴突到达其靶区方面发挥着重要作用。神经回路的正确布线依赖于这些分子的精确表达和功能。轴突寻路、生长锥导航、轴突分支和突触形成的缺陷,对中枢神经系统损伤(如脊髓损伤,SCI)后神经元回路的构建和功能有深远的影响,这些损伤会影响 AGM 的表达或活性。现已发现脊髓的上行和下行通路中包含许多 AGM,包括 Netrins、Slits、Semaphorins(Sema)、Ephrins 及其受体。与排斥信号 Slits 和 Semaphorins 不同,后者限制轴突生长并引导轴突远离不合适的位置,Netrins 是吸引人的导向线索,可促进轴突生长和导向。Ephrins 或其受体的表达或活性的改变会导致运动功能和感觉处理缺陷,它们在脊髓中的轴突导向和突触可塑性中发挥着重要作用。在此,我们强调了 AGM 在脊髓上行和下行通路上的表达、功能和机制,这有助于我们确定新的治疗靶点,以改善 SCI 后的轴突再生和功能恢复。