Department of Cellular and Physiological Sciences, Faculty of Medicine, University of British Columbia, Vancouver, British Columbia, Canada.
International Collaboration on Repair Discoveries (ICORD), University of British Columbia, Vancouver, British Columbia, Canada.
Nat Rev Neurosci. 2024 Oct;25(10):649-667. doi: 10.1038/s41583-024-00849-3. Epub 2024 Aug 20.
Mammalian neurons lose the ability to regenerate their central nervous system axons as they mature during embryonic or early postnatal development. Neuronal maturation requires a transformation from a situation in which neuronal components grow and assemble to one in which these components are fixed and involved in the machinery for effective information transmission and computation. To regenerate after injury, neurons need to overcome this fixed state to reactivate their growth programme. A variety of intracellular processes involved in initiating or sustaining neuronal maturation, including the regulation of gene expression, cytoskeletal restructuring and shifts in intracellular trafficking, have been shown to prevent axon regeneration. Understanding these processes will contribute to the identification of targets to promote repair after injury or disease.
哺乳动物神经元在胚胎期或出生后早期发育过程中成熟后,丧失了再生中枢神经系统轴突的能力。神经元成熟需要经历一个从神经元成分生长和组装的状态转变为这些成分固定并参与有效信息传递和计算机制的状态。为了在损伤后再生,神经元需要克服这种固定状态,重新激活其生长程序。已经表明,参与启动或维持神经元成熟的各种细胞内过程,包括基因表达的调节、细胞骨架重构和细胞内运输的转变,都会阻止轴突再生。了解这些过程将有助于确定在损伤或疾病后促进修复的靶点。