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

近年来，我们的团队在阐明中枢神经系统（CNS）慢性炎症的神经病理机制和动力学方面做出了重大贡献。然而，病理仍未完全阐明，并且仍然缺乏阻断中枢神经系统损伤过程的治疗策略。该项目提案基于我们未发表的数据，表明嗜前eurotrophin受体Sortilin在中枢神经系统自身免疫反应的定性和定量组成和调节中起关键作用。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。我们将通过分析中枢神经系统细胞与免疫细胞中组成性和条件性Sortilin敲除以及条件性Sortilin过表达对EAE起始和慢性化的影响来研究Sortilin (i)，以及（ii）与健康供者相比，MS患者中Sortilin的影响。

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 This project proposal is based on our unpublished data indicating a critical role for the proneurotrophin-receptor Sortilin in the qualitative and quantitative composition and regulation of autoimmune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.