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Tissue Plasminogen Activator and Neuronal Degeneration

组织纤溶酶原激活剂和神经元变性

基本信息

批准号：
6786675
负责人：
SIDNEY STRICKLAND
金额：
$ 41.75万
依托单位：
ROCKEFELLER UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
1997
资助国家：
美国
起止时间：
1997-06-01 至 2007-08-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/6786675
关键词：
extracellular matrix fibrin gene targeting hippocampus laboratory mouse laboratory rat microglia nerve injury nervous system regeneration neural degeneration neurons plasminogen activator protein structure function sciatic nerve

项目摘要

DESCRIPTION (provided by applicant): The protease tissue plasminogen activator (tPA) has been implicated in neuronal death in the central nervous system (CNS). We have now found that tPA also affects neurons after damage in the peripheral nervous system (PNS). In the mouse sciatic nerve, tPA is up-regulated by Schwann cells after crush injury, suggesting a role in either protecting the tissue or contributing to the damage. To investigate this question, we examined mice that lack either tPA or plasminogen. Both genotypes have exacerbated damage after crush, indicating that the tPA/plasminogen system is a beneficial response of the tissue to injury. We have also found that fibrin is extensively deposited in the injured nerve. Removal of fibrin genetically or pharmacologically from mice protects their sciatic nerve from the increased injury observed in the absence of tPA or plasminogen. These results indicate that the role of the tPAlplasminogen system is to clear fibrin from the injured nerve. We have also found that fibrin deposition inhibits the regenerative phase after injury. This application proposes to extend this work by: 1), determining themechanism by which fibrin deposition inhibits sciatic nerve regeneration; 2) analyzing the role of the tPA/plasminogen system in mouse and rat models of CNS degeneration in great detail; and 3) evaluating new methods for fibrin removal as therapeutic strategies to reduce nerve damage and promote regeneration.

描述（由申请人提供）：蛋白酶组织纤溶酶原激活剂

项目成果

期刊论文数量（29）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Neuronal death in the central nervous system demonstrates a non-fibrin substrate for plasmin.

中枢神经系统中的神经元死亡表明纤溶酶具有非纤维蛋白底物。

DOI：
10.1073/pnas.94.18.9779
发表时间：
1997
期刊：
Proceedings of the National Academy of Sciences of the United States of America
影响因子：
11.1
作者：
Tsirka,SE;Bugge,TH;Degen,JL;Strickland,S
通讯作者：
Strickland,S

Modulation of sympathetic activity by tissue plasminogen activator is independent of plasminogen and urokinase.

组织纤溶酶原激活剂对交感神经活性的调节不依赖于纤溶酶原和尿激酶。

DOI：
10.1124/jpet.107.121335
发表时间：
2007
期刊：
The Journal of pharmacology and experimental therapeutics
影响因子：
0
作者：
Schaefer,Ulrich;Vorlova,Sandra;Machida,Takuji;Melchor,JerryP;Strickland,Sidney;Levi,Roberto
通讯作者：
Levi,Roberto

Cortical deficiency of laminin gamma1 impairs the AKT/GSK-3beta signaling pathway and leads to defects in neurite outgrowth and neuronal migration.