Managing calcineurin inhibitor-induced nephrotoxicity for renoprotection (C04)

管理钙调神经磷酸酶抑制剂诱导的肾毒性以保护肾脏 (C04)

• 批准号: 418410806
• 金额: --
• 依托单位: Institut für Funktionelle Anatomie
• 依托单位国家: 德国
• 项目类别: Collaborative Research Centres
• 财政年份: 2019
• 资助国家: 德国
• 起止时间: 2018-12-31 至 2022-12-31
• 项目状态: 已结题
• 来源: https://gepris.dfg.de/gepris/projekt/418410806?language=en
• 关键词: Managing; calcineurin; inhibitor; induced; nephrotoxicity

Calcineurin inhibitors such as cyclosporin A and tacrolimus are first-line immunosuppressive drugs widely used to prevent rejection of transplanted organs. Despite their success, nephrotoxic side effects such as damage of the glomeruli, vasculature, and tubulointerstitium are common. Here, drugs may affect proteostasis by causing cell stress and maladaption of the pathways of protein quality control. A disequilibrium between cytoprotective and proapoptotic responses may result. This project aims at understanding the functions of cellular proteostasis under calcineurin inhibition, and at discovering renoprotective strategies such as the application of small molecular chaperones.

钙调磷酸酶抑制剂如环孢素A和他克莫司是一线免疫抑制药物，广泛用于预防器官移植排斥反应。尽管取得了成功，但肾小球、脉管系统和小管间质损伤等肾毒性副作用是常见的。在这里，药物可能通过引起细胞应激和蛋白质质量控制途径的不适应来影响蛋白质稳态。可能导致细胞保护反应和促凋亡反应之间的不平衡。本项目旨在了解钙调神经磷酸酶抑制下细胞蛋白酶的功能，并发现小分子伴侣的应用等肾保护策略。