Astrocytic and microglial activation, collectively termed neuroinflammation, is common to most neuropathologies and often exacerbates brain damage. Thus, to improve understanding and treatment of many neuropathologies, it is critical to identify the signals regulating astrocytic and microglial responses. Protease-activated receptor-2 (PAR-2) is well-known to exacerbate peripheral tissue inflammation and immune-related pathologies such as asthma and allergies. While PAR-2 and its activators can increase in the brain following injury, it is unknown whether PAR-2 activation affects inflammation in the CMS. In light of evidence from studies in the periphery, we hypothesize that PAR-2 exacerbates neuroinflammation through its effects on astrocytic and microglial functions. We propose to examine the functional effects of PAR-2 activation on astrocytes and microglia and identify critical intracellular signaling pathways involved in these effects. If this receptor indeed regulates astrocytes and microglia, it may serve as a candidate therapeutic target for managing neuroinflammation. ? ?

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Predoctoral Individual National Research Service Award (F31)
Project #
1F31NS054515-01A1
Application #
7157917
Study Section
Special Emphasis Panel (ZRG1-F03A-M (20))
Program Officer
Golanov, Eugene V
Project Start
2006-07-01
Project End
2008-06-30
Budget Start
2006-07-01
Budget End
2007-06-30
Support Year
1
Fiscal Year
2006
Total Cost
$44,788
Indirect Cost
Name
Emory University
Department
Pharmacology
Type
Schools of Medicine
DUNS #
066469933
City
Atlanta
State
GA
Country
United States
Zip Code
30322
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Mannaioni, Guido; Orr, Anna G; Hamill, Cecily E et al. (2008) Plasmin potentiates synaptic N-methyl-D-aspartate receptor function in hippocampal neurons through activation of protease-activated receptor-1. J Biol Chem 283:20600-11