Paper Information

Title: 

PARS AND THE PATHOGENESIS OF NEURODEGENERATIVE DISORDERS

Type: POSTER
Author(s): FARSHI N.*
 
 *
 
Name of Seminar: IRANIAN CONGRESS OF PHYSIOLOGY AND PHARMACOLOGY
Type of Seminar:  CONGRESS
Sponsor:  PHYSIOLOGY AND PHARMACOLOGY SOCIETY, MASHHAD UNIVERSITY OF MEDICAL SCIENCE
Date:  2007Volume 18
 
 
Abstract: 

Proteinase-activated receptors (PARs) are a subgroup of G-protein coupled receptors that are widely expressed on neural cells and are recognized for their modulatory properties of inflammation (1, 2, 3). We investigated the role of proteinase-activated receptor-2 (PAR2) in the pathogenesis of two common neurodegenerative/inflammatory disorders, multiple sclerosis (MS) and human immunodeficiency virus (HIV)-associated dementia (HAD) (4). PAR2 expression was enhanced on cortical neurons during HAD and it’s over expression and activation diminished neuronal cell death caused by the HIV-encoded protein, Tat in vitro and in vivo. Moreover, PAR2 knock-out animals showed more severe neuroinflammation and neurobehavioral deficits caused by Tat neurotoxicity compared to their wild-type littermates (5). Unlike HAD, PAR2 expression was increased on astrocytes and infiltrating macrophages in CNS in human MS and murine experimental autoimmune encephalomyelitis (EAE), a widely studied animal model of MS. PAR2 activation in macrophages resulted in the release of soluble oligodendrocyte cytotoxins with PAR2 knock-out animals exhibiting a milder EAE disease associated with less T cell reactivity and neuroinflammation compared to their wild-type littermates (6). While these findings suggest a neuroprotective role for neuronal PAR2 in the context of virus-induced brain disease, expression and activation of this receptor on monocytoid cells contributes to neuroinflammation in autoimmune demyelinating disorders, implying alternative roles for PAR2 and its activating proteases depending on the cell type and the mechanism of neuroinflammation.

 
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