Title:Protease-Activated Receptor 2: Are Common Functions in Glial and Immune Cells Linked to Inflammation-Related CNS Disorders?
Volume: 17
Issue: 16
Author(s): Trevor J. Bushell, Margaret R. Cunningham, Kathryn A. McIntosh, Serge Moudio and Robin Plevin
Affiliation:
Keywords:
PAR2, CNS disorders, glia, immune cells, inflammation, neurons.
Abstract: Protease-activated receptors (PARs) are a novel family of G-protein coupled
receptors (GPCRs) whose activation requires the cleavage of the N-terminus by a
serine protease. However, recent evidence reveals that alternative routes of activation
also occur, that PARs signal via multiple pathways and that pathway activation is activator-
dependent. Given our increased understanding of PAR function both under
physiological and pathophysiological conditions, one aspect that has remained constant
is the link between PAR2 and inflammation. PAR2 is expressed in immune cells
of both the innate and adaptive immune system and has been shown to play a role in
several peripheral inflammatory conditions. PAR2 is similarly expressed on astrocytes
and microglia within the CNS and its activation is either protective or detrimental to
CNS function depending on the conditions or disease state investigated. With a clear similarity between
the function of PAR2 on both immune cells and CNS glial cells, here we have reviewed their roles in
both these systems. We suggest that the recent development of novel PAR2 modulators, including those
that show biased signalling, will further increase our understanding of PAR2 function and the development
of potential therapeutics for CNS disorders in which inflammation is proposed to play a role.
