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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Conference Article|
April 01 2002
Tissue plasminogen activator as a modulator of neuronal survival and function
S. E. Tsirka
S. E. Tsirka
1
1Department of Pharmacological Sciences, University Medical Center at Stony Brook, Stony Brook, NY 11794-8651, U.S.A.
1e-mail stella@pharm.sunysb.edu
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Publisher: Portland Press Ltd
Received:
November 19 2001
Online ISSN: 1470-8752
Print ISSN: 0300-5127
© 2002 Biochemical Society
2002
Biochem Soc Trans (2002) 30 (2): 222–225.
Article history
Received:
November 19 2001
Citation
S. E. Tsirka; Tissue plasminogen activator as a modulator of neuronal survival and function. Biochem Soc Trans 1 April 2002; 30 (2): 222–225. doi: https://doi.org/10.1042/bst0300222
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