Strategies for therapeutic targeting of the Aldosterone-Mineralocorticoid Receptor signaling pathway

醛固酮-盐皮质激素受体信号通路靶向治疗策略

• 批准号: 470188766
• 负责人: Privatdozent Dr. Achim Lother
• 金额: --
• 依托单位: Abteilung II
• 依托单位国家: 德国
• 项目类别: Scientific Networks
• 资助国家: 德国
• 项目状态: 未结题
• 来源: https://gepris.dfg.de/gepris/projekt/470188766?language=en
• 关键词: Strategies; therapeutic; targeting; Aldosterone; Mineralocorticoid

The physiological role of aldosterone is to control salt-water homeostasis by acting on the mineralocorticoid receptor (MR) in renal epithelial cells. However, in the past years, a number of studies covering the full spectrum from basic science to clinical trials indicated a role for MR in a broader range of pathological conditions and the reciprocal dependence of different organ systems. These include widespread diseases such as chronic kidney disease, diabetes mellitus, lung disease, liver disease, or cancer that are associated with substantial morbidity and mortality in Germany and the EU. Exploring the therapeutic potential of targeting the aldosterone-MR signaling pathway is therefore timely and of high socioeconomic impact. Currently available MR antagonists are already well established in the treatment of chronic heart failure but their use is limited by substantial adverse effects, e.g. hyperkalemia. Innovative approaches for therapeutic targeting are needed that should be specific for the MR signaling pathway and selectively aiming at its pathological effects in the relevant tissues and cell types. The aim of this scientific network is to connect scientific activities in Germany and the EU to achieve a synergistic output concerning MR research. To this end, we will develop a structured training program for early stage researchers in the aldosterone-MR field. The interdisciplinary nature of this venture requires close collaboration of researchers from different backgrounds. We will bring together basic scientists with translational or clinical researchers to foster exchange, establish new interactions, and initiate collaborative research projects. Together, we will propose a roadmap of how to move from MR-related basic to translational research and discuss the clinical application of MR antagonists in new indications.

醛固酮的生理作用是通过作用于肾上皮细胞中的盐皮质激素受体（MR）来控制盐水稳态。然而，在过去的几年中，许多研究涵盖了从基础科学到临床试验的全方位，表明MR在更广泛的病理条件和不同器官系统的相互依赖性中的作用。这些疾病包括在德国和欧盟与大量发病率和死亡率相关的广泛疾病，如慢性肾病、糖尿病、肺病、肝病或癌症。因此，探索靶向醛固酮-MR信号通路的治疗潜力是及时的，具有很高的社会经济影响。目前可用的MR拮抗剂在慢性心力衰竭的治疗中已经得到很好的确立，但它们的使用受到实质性不良反应（例如高钾血症）的限制。需要创新的治疗靶向方法，这些方法应该对MR信号通路具有特异性，并选择性地针对其在相关组织和细胞类型中的病理作用。该科学网络的目的是将德国和欧盟的科学活动联系起来，以实现有关MR研究的协同产出。为此，我们将为醛固酮-MR领域的早期研究人员制定一个结构化的培训计划。这项事业的跨学科性质需要来自不同背景的研究人员的密切合作。我们将把基础科学家与转化或临床研究人员聚集在一起，以促进交流，建立新的互动，并启动合作研究项目。我们将共同提出如何从MR相关基础研究转向转化研究的路线图，并讨论MR拮抗剂在新适应症中的临床应用。