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

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 This project proposal is based on our unpublished data indicating a critical role for the proneurotrophin-receptor Sortilin in the qualitative and quantitative composition and regulation of autoimmune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