National Institute of Pharmaceutical Education and Research, Ahmedabad, Opposite Air Force Station, Palaj, Gandhinagar, Gujarat 382355, India.
ACS Chem Neurosci. 2022 May 4;13(9):1358-1369. doi: 10.1021/acschemneuro.2c00189. Epub 2022 Apr 22.
Disturbance in the neuronal network leads to instability in the microtubule (MT) railroad of axons, causing hindrance in the intra-axonal transport and making it difficult to re-establish the broken network. Peripheral nervous system (PNS) neurons can stabilize their MTs, leading to the formation of regeneration-promoting structures called "growth cones". However, central nervous system (CNS) neurons lack this intrinsic reparative capability and, instead, form growth-incompetent structures called "retraction bulbs", which have a disarrayed MT network. It is evident from various studies that although axonal regeneration depends on both cell-extrinsic and cell-intrinsic factors, any therapy that aims at axonal regeneration ultimately converges onto MTs. Understanding the neuronal MT dynamics will help develop effective therapeutic strategies in diseases where the MT network gets disrupted, such as spinal cord injury, traumatic brain injury, multiple sclerosis, and amyotrophic lateral sclerosis. It is also essential to know the factors that aid or inhibit MT stabilization. In this review, we have discussed the MT dynamics postaxotomy in the CNS and PNS, and factors that can directly influence MT stability in various diseases.
神经元网络的紊乱会导致轴突微管（MT）轨道不稳定，从而阻碍轴内运输，难以重新建立断裂的网络。周围神经系统（PNS）神经元可以稳定其 MT，形成促进再生的结构，称为“生长锥”。然而，中枢神经系统（CNS）神经元缺乏这种内在的修复能力，而是形成生长能力差的结构，称为“回缩球”，其 MT 网络杂乱无章。从各种研究中可以明显看出，尽管轴突再生依赖于细胞外和细胞内因素，但任何旨在促进轴突再生的治疗方法最终都集中在 MT 上。了解神经元 MT 动力学将有助于在 MT 网络受到破坏的疾病中开发有效的治疗策略，例如脊髓损伤、创伤性脑损伤、多发性硬化症和肌萎缩侧索硬化症。了解有助于或抑制 MT 稳定性的因素也很重要。在这篇综述中，我们讨论了 CNS 和 PNS 中轴突切断后的 MT 动力学，以及各种疾病中直接影响 MT 稳定性的因素。
