Minor Kenneth, Phillips Jacob, Seeds Nicholas W
Department of Biochemistry & Molecular Genetics, University of Colorado Denver, School of Medicine, Aurora, Colorado 8004, USA.
J Neurochem. 2009 May;109(3):706-15. doi: 10.1111/j.1471-4159.2009.05977.x. Epub 2009 Feb 11.
Following CNS injury, myelin-associated inhibitors represent major obstacles to axonal regeneration and functional recovery. The following study suggests that the proteolytic enzyme tissue plasminogen activator (tPA) plays a major function in 'conditioning-injury induced' axon regeneration. In this paradigm, prior peripheral nerve injury leads to an enhanced ability of sensory neurons to regenerate their central axons in the presence of the CNS inhibitory microenvironment. tPA is widely expressed by CNS and PNS neurons and plays major roles in synaptic reorganization and plasticity. This study shows that cultured neurons from mice deficient in tPA, in contrast to wild-type mice, fail to undergo conditioning-injury induced axonal regeneration in the presence of purified myelin membranes. Interestingly, neurons from mice deficient in plasminogen, the best known substrate for tPA, showed active axon regeneration. These results suggest a novel plasminogen-independent role for tPA in promoting axonal regeneration on CNS myelin.
中枢神经系统损伤后，髓鞘相关抑制因子是轴突再生和功能恢复的主要障碍。以下研究表明，蛋白水解酶组织型纤溶酶原激活剂（tPA）在“条件性损伤诱导”的轴突再生中起主要作用。在这种模式下，先前的外周神经损伤会使感觉神经元在中枢神经系统抑制性微环境存在的情况下，增强其中枢轴突再生的能力。tPA在中枢神经系统和外周神经系统神经元中广泛表达，并在突触重组和可塑性中起主要作用。这项研究表明，与野生型小鼠相比，来自tPA缺陷小鼠的培养神经元在存在纯化髓鞘膜的情况下，无法进行条件性损伤诱导的轴突再生。有趣的是，来自纤溶酶原缺陷小鼠的神经元，纤溶酶原是tPA最著名的底物，却显示出活跃的轴突再生。这些结果表明tPA在促进中枢神经系统髓鞘上的轴突再生方面具有一种新的不依赖纤溶酶原的作用。
