Role of Protease-Activated Receptor-2 in Reactive Glia

蛋白酶激活受体 2 在反应性胶质细胞中的作用

• 批准号: 7157917
• 负责人: ANNA GOLDSHMIDT ORR
• 金额: $ 4.48万
• 依托单位: EMORY UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-07-01 至 2008-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7157917
• 关键词: astrocytes; brain; endopeptidases; glia; human; inflammation; microglia; receptor; role

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.

描述（由申请人提供）：星形胶质细胞和小胶质细胞活化，统称为神经炎症，是大多数神经病理学的常见现象，通常会加重脑损伤。因此，为了提高对许多神经病理学的理解和治疗，识别调节星形胶质细胞和小胶质细胞反应的信号是至关重要的。众所周知，蛋白酶激活受体-2（PAR-2）会加剧外周组织炎症和免疫相关的病理，如哮喘和过敏。虽然PAR-2及其激活剂可以在损伤后在脑中增加，但PAR-2激活是否影响CMS中的炎症尚不清楚。根据来自外周研究的证据，我们假设PAR-2通过其对星形胶质细胞和小胶质细胞功能的影响而加剧神经炎症。我们建议检查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，它可能作为一个候选的治疗目标，用于管理神经炎症。