Additional evidence that the sympathetic nervous system regulates the vessel wall release of tissue plasminogen activator

SummaryAlthough conventionally associated with fibrin clot degradation, recent work has uncovered new functions for the tissue plasminogen activator (tPA)/plasminogen cascade in central nervous system physiology and pathology. This extracellular proteolytic cascade has been shown to have roles in learning and memory, stress, neuronal degeneration, addiction and Alzheimer’s disease. The current review considers the different ways tPA functions in the brain.

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Beyond Clot Dissolution; Role of Tissue Plasminogen Activator in Central Nervous System

Biomolecules & Therapeutics ◽

10.4062/biomolther.2007.15.1.016 ◽

2007 ◽

Vol 15 (1) ◽

pp. 16-26

Author(s):

Ji-Woon Kim ◽

Soon-Young Lee ◽

So-Hyun Joo ◽

Mi-Ryoung Song ◽

Chan-Young Shin

Keyword(s):

Central Nervous System ◽

Nervous System ◽

Plasminogen Activator ◽

Tissue Plasminogen Activator ◽

Tissue Plasminogen

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Tissue plasminogen activator as a modulator of neuronal survival and function

Biochemical Society Transactions ◽

10.1042/bst0300222 ◽

2002 ◽

Vol 30 (2) ◽

pp. 222-225 ◽

Cited By ~ 51

Author(s):

S. E. Tsirka

Keyword(s):

Central Nervous System ◽

Extracellular Matrix ◽

Nervous System ◽

Neurite Outgrowth ◽

Plasminogen Activator ◽

Tissue Plasminogen Activator ◽

Cell Surface Receptor ◽

Mammalian Brain ◽

Tissue Plasminogen ◽

Surface Receptor

The tissue plasminogen activator (tPA)/plasmin proteolytic system has been implicated in both physiological and pathological processes in the mammalian brain. The physiological roles include facilitating neurite outgrowth and pathfinding. The pathological role involves mediating a critical step in the progression of excitotoxin-induced neurodegeneration. Mechanistically, tPA appears to function through two pathways. The first pathway proceeds via its well established ability to convert plasminogen into plasmin. Plasmin then either promotes neuronal death via both the degradation of the extracellular matrix and the establishment of chemoattractant gradients for microglia, or facilitates neurite outgrowth through the processing of extracellular matrix proteoglycans. The second pathway for tPA does not involve its proteolytic activity: rather tPA functions as an agonist to stimulate a cell-surface receptor on microglia (the macrophage-like immunocompetent cells of the central nervous system) and results in their activation. Once activated after neuronal injury, microglia contribute to the ensuing neurodegeneration. Using tPA as a link between neurons and microglia, we are focusing on understanding their communication and interactions in the normal and diseased central nervous system.

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Expression of Neuroserpin, an Inhibitor of Tissue Plasminogen Activator, in the Developing and Adult Nervous System of the Mouse

Journal of Neuroscience ◽

10.1523/jneurosci.17-23-08984.1997 ◽

1997 ◽

Vol 17 (23) ◽

pp. 8984-8996 ◽

Cited By ~ 110

Author(s):

Stefan R. Krueger ◽

Gian-Piero Ghisu ◽

Paolo Cinelli ◽

Thomas P. Gschwend ◽

Thomas Osterwalder ◽

...

Keyword(s):

Nervous System ◽

Plasminogen Activator ◽

Tissue Plasminogen Activator ◽

Tissue Plasminogen

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Tissue Plasminogen Activator in Nervous System Function and Dysfunction

Thrombosis and Haemostasis ◽

10.1055/s-0037-1616210 ◽

2001 ◽

Vol 86 (07) ◽

pp. 138-143 ◽

Cited By ~ 34

Author(s):

Sidney Strickland

Keyword(s):

Nervous System ◽

Plasminogen Activator ◽

Tissue Plasminogen Activator ◽

In Vivo Models ◽

Knock Out ◽

Tissue Plasminogen ◽

Culture Models ◽

Nervous System Function ◽

Knock Out Mice

SummaryThe extracellular protease tissue plasminogen activator (tPA) has been implicated in various normal and pathological situations in the mammalian nervous system. The availability of (i) transgenic and knock-out mice in which the expression level of tPA can be widely varied, (ii) in vivo models for studying function and disease, and (iii) culture models for examining cell behavior, has allowed a detailed evaluation of many of these proposed functions. This chapter summarizes the current state of knowledge of possible roles for the tPA/plasminogen system in neuronal function and dysfunction.

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