Critical contribution of proneurotrophin-receptor Sortilin to the pathology of multiple sclerosis and experimental autoimmune encephalomyelitis

原神经营养蛋白受体分拣蛋白对多发性硬化症和实验性自身免疫性脑脊髓炎病理学的重要贡献

• 批准号: 191931699
• 负责人: Professor Dr. Thomas E. Willnow
• 金额: --
• 依托单位: Klinik und Poliklinik für Neurologie
• 依托单位国家: 德国
• 项目类别: Research Grants
• 财政年份: 2011
• 资助国家: 德国
• 起止时间: 2010-12-31 至 2014-12-31
• 项目状态: 已结题
• 来源: https://gepris.dfg.de/gepris/projekt/191931699?language=en
• 关键词: Critical; contribution; proneurotrophin; receptor; Sortilin

In recent years, our group has contributed significantly to the elucidation of mechanisms and kinetics of neuronal pathology in chronic inflammation of the central nervous system (CNS). However, the pathology is still not fully elucidated yet and treatment strategies to block the damage processes within the CNS are still lacking. This project proposal is based on our unpublished data indicating a critical role for the proneurotrophin-receptor Sortilin in the qualitative and quantitative composition and regulation of autoimmune reactions in the CNS. The aim is to characterize this system both in the course of multiple sclerosis (MS) and its animal model experimental autoimmune encephalomyelitis (EAE). We will investigate Sortilin (i) by analyzing the impact of both a constitutive and a conditional Sortilin knockout as well as a conditional Sortilin overexpression in CNS cells vs. immune cells on the initiation and chronification of EAE, and (ii) in patients with MS, as compared to healthy donors.

近年来，我们的小组作出了重大贡献，阐明机制和动力学的神经病理慢性炎症的中枢神经系统（CNS）。然而，病理学仍未完全阐明，并且仍然缺乏阻断CNS内损伤过程的治疗策略。该项目提案是基于我们未发表的数据，表明前神经营养素受体分拣蛋白在CNS自身免疫反应的定性和定量组成和调节中的关键作用。目的是在多发性硬化症（MS）及其动物模型实验性自身免疫性脑脊髓炎（EAE）的过程中表征该系统。我们将研究分拣蛋白（i）通过分析CNS细胞相对于免疫细胞中组成型和条件性分拣蛋白敲除以及条件性分拣蛋白过表达对EAE的起始和慢性化的影响，和（ii）与健康供体相比，在MS患者中。

项目成果

Role of Sortilin in Models of Autoimmune Neuroinflammation

• DOI: 10.4049/jimmunol.1403156
• 发表时间: 2015-12-15
• 期刊: JOURNAL OF IMMUNOLOGY
• 影响因子: 4.4
• 作者: Reuter, Eva;Weber, Juliane;Zipp, Frauke
• 通讯作者: Zipp, Frauke