The Neuroprotective Mechanism of IGF-2 in Neuromyelitis optica spectrum disorder

Background: Neuromyelitis optica spectrum disorder (NMOSD) is an immune-mediated inflammatory demyelinating disease and AQP4 antibody (AQP4-IgG or NMO-IgG) is the major cause of NMOSD. However，Many of the underlying molecular mechanisms in the occurrence and development of NMOSD disease are not completely understood. Insulin-like growth factor-2 (IGF-2) is a multifunctional cell proliferation regulator which plays an essential role in early embryonic development. Recent studies have shown that IGF-2 has a crucial effect on memory and learning function in the brain and has a neuroprotective function. In this study, we investigated IGF-2 the neuroprotective effect of IGF-2 in NMOSD. Metheds: The proteomic analysis of serum proteins of NMOSD patients and normal persons was carried out, and significant differential proteins were found. The screened differential proteins were verified and analyzed, and their roles in the pathogenesis of NMOSD were studied in vivo and in vitro. Results: : In this study, we found a significant down-regulation of IGF-2 in serum of patients with the NMOSD compared with the normal group, through a serum proteomic analysis of clinical patients. Our results revealed that IGF-2 could reduce AQP4-IgG-induced apoptosis and inflammation in astrocytes by activating IGF-1R and PI3K/AKT signaling pathway in vitro. Overexpression of IGF-2 in astrocytes reduced the effect of AQP4-IgG on astrocyte glutamate uptake. In addition, the administration of IGF-2 could improve pathological changes in the CNS of injured mice model. Conclusion: In this study, we found that IGF-2 could be a potential target for diagnosis and treatment of NMOSD.