生物谷： 来自加州大学San Diego分校（UCSD）医学院的科学家最近发现，纤维原蛋白——一种存在于循环系统中的凝血蛋白——会阻碍中枢神经系统神经细胞的生长，而这些细胞的生长对于受伤后的脊髓再生非常关键。研究结果或许能解释为什么人类在脊髓受伤后无法自我修复。
研究负责人是UCSD药理学系助理教授Katerina Akassoglou，她的发现首次证实，当血液进入神经系统后，血液蛋白将阻碍神经自我修复。结果发表在7月2日的《Proceedings of the National Academy of Sciences》上。
研究小组分析了老鼠中3种主要脊髓损伤，它们都造成了细胞和血管破损，因此血液中纤维原蛋白渗入到神经系统中。一旦受伤，由于大脑和脊髓中存在多种抑制分子，所以神经细胞无法修复，最终导致患者瘫痪。科学家惊讶的发现纤维原蛋白大量聚集在受伤区域。这使得小组开始研究凝血蛋白对神经细胞再生能力的影响。
Akassoglou说：“结果显示，凝血蛋白直接影响神经细胞再生能力。”含有纤维原蛋白的血液一旦渗入到受伤区域，凝血蛋白就会通过结合到β3受体来阻止轴突生长。这种结合会激活另一个受体，从而起到阻碍的作用。
以上结果或许能为脊髓受伤的患者带来康复的新希望，确认其中特定的抑制分子能使得被破坏的神经再生，从而让病人从瘫痪中得以恢复。而且同样的机制还可能存在于其它疾病中，例如多发性硬化及出血性中风等。（引自教育部科技发展中心）
原始出处:
Published online before print July 2, 2007
Proc. Natl. Acad. Sci. USA, 10.1073/pnas.0704045104
Neuroscience
Fibrinogen inhibits neurite outgrowth via 3 integrin-mediated phosphorylation of the EGF receptor
( blood-brain barrier | regeneration | spinal cord injury | transactivation | scar )
Christian Schachtrup *, Paul Lu , Leonard L. Jones , Jae K. Lee , Jerry Lu *, Ben D. Sachs *, Binhai Zheng , and Katerina Akassoglou *
Departments of *Pharmacology and Neurosciences, University of California at San Diego, La Jolla, CA 92093
Edited by Hans Thoenen, Max Planck Institute of Neurobiology, Martinsried, Germany, and approved May 31, 2007 (received for review May 1, 2007)
Changes in the molecular and cellular composition of the CNS after injury or disease result in the formation of an inhibitory environment that inhibits the regeneration of adult mammalian CNS neurons. Although a dramatic change in the CNS environment after traumatic injury or disease is hemorrhage because of vascular rupture or leakage of the blood-brain barrier, the potential role for blood proteins in repair processes remains unknown. Here we show that the blood protein fibrinogen is an inhibitor of neurite outgrowth that is massively deposited in the spinal cord after injury. We show that fibrinogen acts as a ligand for 3 integrin and induces the transactivation of EGF receptor (EGFR) in neurons. Fibrinogen-mediated inhibition of neurite outgrowth is reversed by blocking either 3 integrin or phoshorylation of EGFR. Inhibition of Src family kinases that mediate the cross-talk between integrin and growth factor receptors rescue the fibrinogen-induced phosphorylation of EGFR. These results identify fibrinogen as the first blood-derived inhibitor of neurite outgrowth and suggest fibrinogen-induced EGFR transactivation on neuronal cells as a molecular link between vascular and neuronal damage in the CNS after injury.
