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对某些血液成分进行调整会在神经系统中产生不同的功能。

Tinkering with certain blood components can engender distinct functions in the nervous system.

作者信息

Monard D

机构信息

Friedrich Miescher-Institut, Basel, Switzerland.

出版信息

Perspect Dev Neurobiol. 1993;1(3):165-8.

PMID:8087541
Abstract

A 43 kd protein called glia-derived nexin or protease nexin-1 (GDN/PN-1) with both neurite-promoting and serine protease inhibitor activity is developmentally regulated during the differentiation of the nervous system. The synthesis of GDN/PN-1 remains high in structures such as the olfactory system where degeneration and regeneration take place throughout life. It is also up-regulated following injury both in the peripheral and the central nervous systems. Together with hirudin (a protease inhibitor from the leech), GDN/PN-1 is the most potent thrombin inhibitor known today. The surprising discovery of this potent thrombin inhibitor in the nervous system led to demonstration that mRNAs coding for prothrombin and the thrombin receptor are detected in neural tissue. Neuronal cells can cleave the inactive prothrombin into the active thrombin, which, in turn, specifically cleaves its own receptor to trigger a metabolic cascade causing sudden neurite retraction. Other macromolecules, such as vitronectin and thrombospondin, also found in the blood, can stimulate neurite outgrowth. Altogether, the data available today indicate that many molecules considered until now to be components of the hematopoietic system could perform distinct tasks and specific functions in the nervous system. Some of the experimental facts still required for demonstration of this hypothesis are discussed.

摘要

一种名为神经胶质衍生的凝血酶结合蛋白或蛋白酶nexin-1(GDN/PN-1)的43千道尔顿蛋白质,具有促进神经突生长和丝氨酸蛋白酶抑制活性,在神经系统分化过程中受到发育调控。GDN/PN-1的合成在诸如嗅觉系统等结构中仍保持高水平,在这些结构中,终生都发生退化和再生。在周围神经系统和中枢神经系统损伤后,它也会上调。与水蛭素(一种来自水蛭的蛋白酶抑制剂)一起,GDN/PN-1是目前已知的最有效的凝血酶抑制剂。在神经系统中发现这种强效凝血酶抑制剂这一惊人发现,导致了在神经组织中检测到编码凝血酶原和凝血酶受体的mRNA的证明。神经元细胞可以将无活性的凝血酶原切割成有活性的凝血酶,而凝血酶又会特异性地切割其自身受体,从而引发代谢级联反应,导致神经突突然回缩。其他在血液中也能找到的大分子,如玻连蛋白和血小板反应蛋白,可刺激神经突生长。总之,目前可得的数据表明,许多迄今为止被认为是造血系统组成部分的分子,可能在神经系统中执行不同的任务和特定的功能。本文讨论了证明这一假设仍需要的一些实验事实。

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引用本文的文献

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Mice lacking protease nexin-1 show delayed structural and functional recovery after sciatic nerve crush.缺乏蛋白酶连接素-1的小鼠在坐骨神经挤压后结构和功能恢复延迟。
J Neurosci. 2007 Apr 4;27(14):3677-85. doi: 10.1523/JNEUROSCI.0277-07.2007.
2
Progressive neuronal and motor dysfunction in mice overexpressing the serine protease inhibitor protease nexin-1 in postmitotic neurons.在有丝分裂后神经元中过表达丝氨酸蛋白酶抑制剂蛋白酶nexin-1的小鼠中出现进行性神经元和运动功能障碍。
J Neurosci. 2001 Nov 15;21(22):8830-41. doi: 10.1523/JNEUROSCI.21-22-08830.2001.
3
Thrombomodulin as a new marker of lesion-induced astrogliosis: involvement of thrombin through the G-protein-coupled protease-activated receptor-1.
血栓调节蛋白作为损伤诱导星形胶质细胞增生的新标志物:凝血酶通过G蛋白偶联蛋白酶激活受体-1的参与。
J Neurosci. 2000 Apr 1;20(7):2543-50. doi: 10.1523/JNEUROSCI.20-07-02543.2000.
4
Calcium mobilization and protease-activated receptor cleavage after thrombin stimulation in motor neurons.运动神经元中凝血酶刺激后的钙动员和蛋白酶激活受体裂解
J Mol Neurosci. 1998 Feb;10(1):31-44. doi: 10.1007/BF02737083.
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Drugs. 1996 Jan;51(1):28-44. doi: 10.2165/00003495-199651010-00004.