Role of Protease-Activated Receptor-2 in Reactive Glia

描述（由申请人提供）：星形胶质细胞和小胶质细胞激活，统称为神经炎症，在大多数神经病变中很常见，通常会加剧脑损伤。因此，为了提高对许多神经病变的理解和治疗，识别调节星形细胞和小胶质细胞反应的信号是至关重要的。众所周知，蛋白酶活化受体-2 （PAR-2）可加剧外周组织炎症和免疫相关病变，如哮喘和过敏。虽然损伤后大脑中PAR-2及其激活物会增加，但尚不清楚PAR-2激活是否会影响CMS中的炎症。根据外周研究的证据，我们假设PAR-2通过其对星形细胞和小胶质细胞功能的影响而加剧神经炎症。我们建议研究PAR-2激活对星形胶质细胞和小胶质细胞的功能影响，并确定参与这些影响的关键细胞内信号通路。如果这种受体确实调节星形胶质细胞和小胶质细胞，它可能作为治疗神经炎症的候选治疗靶点。

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.