Role of Protease-Activated Receptor-2 in Reactive Glia

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DESCRIPTION (provided by applicant): 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.