Involvement of store-operated CRAC channels and mitochondrial Ca2+ dynamics in health and disease.

库操作的 CRAC 通道和线粒体 Ca2 动力学与健康和疾病的关系。

• 批准号: G0601485/1
• 负责人: Anant Parekh
• 金额: $ 76.45万
• 依托单位: University of Oxford
• 依托单位国家: 英国
• 项目类别: Research Grant
• 财政年份: 2008
• 资助国家: 英国
• 起止时间: 2008 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=G0601485%2F1
• 关键词: Involvement; store; operated; CRAC; channels

The last 20 years have seen a marked rise in allergy sufferers in the U.K. Allergies come in various disguises but two particularly common ones are asthma and rhinitis/polyposis. Recent figures indicate that almost 20% of the population suffer, at some time, from rhinitis and polyposis, ailments that result in inflammation within the nose, with serious consequences on quality of life including full nasal obstruction and loss of smell. These disorders arise from a trigger-happy immune system, with the main culprit being the mast cell. Effective treatment requires detailed understanding of fundamental processes in cell biology and the application of this to mast cells may lead to new therapies for combating allergies. It is known that an increase in calcium causes the mast cell to secrete a battery of chemicals that recruit and stimulate other immune cells, blood vessels and airway muscle. If unchecked, this produces substantial local tissue damage. We seek to understand how, at a very fundamental level, calcium signals are controlled and how these contribute to mast cell activation. This work will shed new light on what happens when things go wrong with these cells and may identify novel therapeutic targets for drug therapy for allergic disorders.

过去 20 年，英国过敏症患者显着增加。过敏症有多种表现形式，但其中两种特别常见的是哮喘和鼻炎/息肉病。最近的数据表明，近 20% 的人口在某些时候患有鼻炎和息肉病，这些疾病会导致鼻子内炎症，对生活质量造成严重后果，包括完全鼻塞和嗅觉丧失。这些疾病是由喜欢触发的免疫系统引起的，罪魁祸首是肥大细胞。有效的治疗需要详细了解细胞生物学的基本过程，并将其应用于肥大细胞可能会带来对抗过敏的新疗法。众所周知，钙的增加会导致肥大细胞分泌一系列化学物质，这些化学物质会招募和刺激其他免疫细胞、血管和气道肌肉。如果不加以控制，这会产生严重的局部组织损伤。我们试图从根本上了解钙信号是如何被控制的以及这些信号如何促进肥大细胞激活。这项工作将为了解这些细胞出现问题时发生的情况提供新的线索，并可能确定过敏性疾病药物治疗的新治疗靶点。