Thrombin: A Potential Proinflammatory Mediator in Neurotrauma and Neurodegenerative Disorders

Author(s): Z. Suo, B. A. Citron, B. W. Festoff.

Journal Name: Current Drug Targets - Inflammation & Allergy

Volume 3 , Issue 1 , 2004

Abstract:

Thrombin is well known in its function as the ultimate serine protease in the coagulation cascade. Emerging evidence indicates that thrombin also functions as a potent signaling molecule that regulates physiologic and pathogenic responses alike in a large variety of cell populations and tissues. Accompanying CNS injury and other cerebral vascular damages, prothrombin activation and leakage of active thrombin into CNS parenchyma has been documented. Due to the irreplaceable feature of neurons, overreactive inflammatory reactions in the CNS often cause irreversible neuronal damage. Therefore, particular attention is required to develop strategies that restrict CNS inflammatory responses to beneficial, in contrast to neurotoxic ones. In this regard, thrombin not only activates endothelial cells and induces leukocyte infiltration and edema but also activates astrocytes, and particularly microglia, as recently demonstrated, to propagate the focal inflammation and produce potential neurotoxic effects. Recently revealed molecular mechanisms underlying these thrombin effects appear to involve proteolytic activation of two different thrombin-responsive, protease-activated receptors (PARs), PAR1 and PAR4, possibly in concert. Potential therapeutic strategies based on appreciation of the current understanding of molecular mechanisms underlying thrombin-induced CNS inflammation are also discussed.

Keywords: thrombin, receptors, agonist peptide, inflammation

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Article Details

VOLUME: 3
ISSUE: 1
Year: 2004
Page: [105 - 114]
Pages: 10
DOI: 10.2174/1568010043483953

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