Format

Send to:

Choose Destination
See comment in PubMed Commons below

Thrombin: a potential proinflammatory mediator in neurotrauma and neurodegenerative disorders.

Author information

  • 1Laboratory for Alzheimer's Disease & Aging Research, Veterans Affairs Medical Center, Kansas City, Missouri and Department of Neurology, University of Kansas Medical School, Kansas City, Kansas, USA. zsuo@kumc.edu

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, over-reactive 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.

PMID:
15032647
[PubMed - indexed for MEDLINE]
PubMed Commons home

PubMed Commons

0 comments
How to join PubMed Commons

    Supplemental Content

    Full text links

    Icon for Bentham Science Publishers Ltd.
    Loading ...
    Write to the Help Desk