生物谷： 來自加州大學(xué)San Diego分校（UCSD）醫(yī)學(xué)院的科學(xué)家最近發(fā)現(xiàn)，纖維原蛋白——一種存在于循環(huán)系統(tǒng)中的凝血蛋白——會(huì)阻礙中樞神經(jīng)系統(tǒng)神經(jīng)細(xì)胞的生長,，而這些細(xì)胞的生長對(duì)于受傷后的脊髓再生非常關(guān)鍵,。研究結(jié)果或許能解釋為什么人類在脊髓受傷后無法自我修復(fù)。
研究負(fù)責(zé)人是UCSD藥理學(xué)系助理教授Katerina Akassoglou,，她的發(fā)現(xiàn)首次證實(shí),，當(dāng)血液進(jìn)入神經(jīng)系統(tǒng)后，血液蛋白將阻礙神經(jīng)自我修復(fù),。結(jié)果發(fā)表在7月2日的《Proceedings of the National Academy of Sciences》上,。
研究小組分析了老鼠中3種主要脊髓損傷，它們都造成了細(xì)胞和血管破損,，因此血液中纖維原蛋白滲入到神經(jīng)系統(tǒng)中,。一旦受傷，由于大腦和脊髓中存在多種抑制分子,，所以神經(jīng)細(xì)胞無法修復(fù),，最終導(dǎo)致患者癱瘓?？茖W(xué)家驚訝的發(fā)現(xiàn)纖維原蛋白大量聚集在受傷區(qū)域,。這使得小組開始研究凝血蛋白對(duì)神經(jīng)細(xì)胞再生能力的影響。
Akassoglou說：“結(jié)果顯示,，凝血蛋白直接影響神經(jīng)細(xì)胞再生能力,。”含有纖維原蛋白的血液一旦滲入到受傷區(qū)域，凝血蛋白就會(huì)通過結(jié)合到β3受體來阻止軸突生長,。這種結(jié)合會(huì)激活另一個(gè)受體,，從而起到阻礙的作用。
以上結(jié)果或許能為脊髓受傷的患者帶來康復(fù)的新希望,，確認(rèn)其中特定的抑制分子能使得被破壞的神經(jīng)再生,，從而讓病人從癱瘓中得以恢復(fù),。而且同樣的機(jī)制還可能存在于其它疾病中，例如多發(fā)性硬化及出血性中風(fēng)等,。（引自教育部科技發(fā)展中心）
原始出處:
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.
