Coordination project: Sphingolipids - Signals and Disease

协调项目：鞘脂 - 信号与疾病

• 批准号: 173176533
• 负责人: Professor Dr. Erich Gulbins
• 金额: --
• 依托单位: Institut für Molekularbiologie
• 依托单位国家: 德国
• 项目类别: Priority Programmes
• 财政年份: 2010
• 资助国家: 德国
• 起止时间: 2009-12-31 至 2014-12-31
• 项目状态: 已结题
• 来源: https://gepris.dfg.de/gepris/projekt/173176533?language=en
• 关键词: Coordination; project; Sphingolipids; Signals; Disease

Until the late 1980s, sphingolipids were believed to be structural components of the cell membrane. However, it has now been established that sphingolipids are essential regulators of many fundamental cellular processes, such as proliferation, survival, cell death, adhesion, migration, and embryogenesis. During the first funding period, projects of the special research program 1267 focused on (i) the sorting, regulation, and cellular functions of sphingolipids and the enzymes mediating sphingolipid metabolism and (ii) the role of sphingolipids in the cardiorenovascular system (ischemic heart infarcts, atherosclerosis, coagulation, diabetic nephropathy, and fibrosis), in the immune system, in neuropsychiatric diseases (Alzheimer disease, major depression), in inflammatory and infectious diseases (sepsis, acute lung failure, cystic fibrosis, bacterial and viral infections), and in autoimmune disorders (multiple sclerosis). (iii) Several projects have already transferred insights from basic science and preclinical models into novel clinical studies, thereby proving the very successful translational aspect of the present special research program. During the second funding period of the special research program, projects will focus on translating insights from the biochemistry, biophysics, and cell biology of sphingolipids into preclinical animal models and, finally, clinical studies. Basic science projects in the special research program will investigate the topology of sphingolipids, the regulation of the primary enzymes involved in lipid sphingolipid metabolism, and the regulation and function of sphingolipid receptors. However, the focus of the special research program will be the characterization of the biomedical functions of sphingolipids in diseases of the cardiorenovascular system, the lung, the immune system and in neuropsychiatric disorders. Diseases that are studied in the special research program include coronary artery disease and arteriosclerosis, myocardial infarction, renal fibrosis, diabetic nephropathy, inflammatory diseases, autoimmune disorders such as multiple sclerosis, Alzheimer disease, major depression, mechanisms of acute lung injury, bacterial infections of the lung, cystic fibrosis, and sepsis. Animal models will serve as proof of principle and as preclinical models for developing novel treatment strategies based on the manipulation of sphingolipids in these diseases. The transfer of novel concepts about the biochemical and biological functions of sphingolipids into clinical trials will be continued. Several new clinical trials will be conducted during the second funding period; these trials will be aimed at developing novel treatments and diagnostic methods for multiple sclerosis, cystic fibrosis, cardiovascular diseases, major depression, inflammatory skin disorders, and coronary artery disease.

直到20世纪80年代末，鞘脂还被认为是细胞膜的结构成分。然而，现在已经证实，鞘脂是许多基本细胞过程的重要调节因子，如增殖、存活、细胞死亡、黏附、迁移和胚胎发生。在第一个资助期内，1267特别研究项目的重点是：(I)鞘脂的分类、调节和细胞功能，以及调节鞘脂代谢的酶；(Ii)鞘脂在心血管系统(缺血性心脏病、动脉粥样硬化、凝血、糖尿病肾病和纤维化)、免疫系统、神经精神疾病(阿尔茨海默病、抑郁症)、炎症和感染性疾病(败血症、急性肺衰竭、囊性纤维化、细菌和病毒感染)以及自身免疫性疾病(多发性硬化症)中的作用。(Iii)几个项目已经将基础科学和临床前模型的见解转化为新的临床研究，从而证明了当前特别研究计划非常成功的翻译方面。在特别研究计划的第二个资助期，项目将集中于将鞘脂的生物化学、生物物理学和细胞生物学的见解转化为临床前动物模型，并最终转化为临床研究。特别研究项目中的基础科学项目将研究鞘脂的拓扑结构，参与脂鞘脂代谢的主要酶的调节，以及鞘脂受体的调节和功能。然而，这项特别研究计划的重点将是鉴定鞘磷脂在心血管系统、肺、免疫系统和神经精神疾病中的生物医学功能。在特别研究计划中研究的疾病包括冠状动脉疾病和动脉硬化、心肌梗死、肾脏纤维化、糖尿病肾病、炎症性疾病、自身免疫性疾病，如多发性硬化症、阿尔茨海默病、严重抑郁症、急性肺损伤机制、肺部细菌感染、囊性纤维化和败血症。动物模型将作为原理证明和临床前模型，以这些疾病的鞘脂操作为基础，开发新的治疗策略。将继续将有关鞘磷脂生物化学和生物学功能的新概念转移到临床试验中。在第二个资助期将进行几项新的临床试验；这些试验旨在开发多发性硬化症、囊性纤维化、心血管疾病、严重抑郁症、炎症性皮肤病和冠状动脉疾病的新疗法和诊断方法。