2. Academic Validation
  3. Therapeutic effects of IGF-2 on NMOSD by inhibiting astrocyte apoptosis through modulation of the IGF-1R/PI3K/AKT signaling pathway

Therapeutic effects of IGF-2 on NMOSD by inhibiting astrocyte apoptosis through modulation of the IGF-1R/PI3K/AKT signaling pathway

  • Sci Rep. 2026 Jan 27;16(1):6312. doi: 10.1038/s41598-026-37456-4.
Yingyu Zhang 1,  Na Xu 2,  Kaikai Yu 3,  Xiaoshuang Wang 1,  Xianhui Jiang 4,  Di Wang 1,  Qiurong Yang 1,  Yaxin Qu 1,  Shuai Wang 1,  Wensen Liu 5,  Xuemei Han 6
Affiliations

Affiliations

  • 1 No.1 Department of Neurology, China-Japan Union Hospital of Jilin University, Changchun, 130000, Jilin, P.R. China.
  • 2 Jilin Medical University, Jilin, 132013, Jilin, P.R. China.
  • 3 Chinese Academy of Agricultural Science Changchun Veterinary Research Institute, Changchun, 130117, Jilin, P.R. China.
  • 4 The Second Hospital of Changchun, Changchun, 130062, Jilin, P.R. China.
  • 5 Chinese Academy of Agricultural Science Changchun Veterinary Research Institute, Changchun, 130117, Jilin, P.R. China. [email protected].
  • 6 No.1 Department of Neurology, China-Japan Union Hospital of Jilin University, Changchun, 130000, Jilin, P.R. China. [email protected].
PMID: 41593135 DOI: 10.1038/s41598-026-37456-4
Abstract

Neuromyelitis optica spectrum disorder (NMOSD) is an autoimmune disease characterized by the presence of antibodies specific to the aquaporins 4 (AQP4) protein. The complexity of its pathogenesis poses significant challenges to treatment, which remains both limited and costly. Consequently, there is an urgent need to elucidate the pathogenesis of NMOSD and to develop novel therapeutic strategies. Here, through a proteomic screen of serum from AQP4-IgG-positive NMOSD patients and a control cohort, we observed a significant downregulation of Insulin-like growth factor 2 (IGF-2) in the serum of AQP4-IgG-positive NMOSD patients and correlated with disease severity. Injecting adenovirus overexpressing IGF-2 into the brains of NMOSD mice reduced microglia, neuroinflammation, and brain injury. Both in vivo and in vitro experiments show IGF-2 activates the IGF-1R/PI3K/Akt pathway, reducing Apoptosis and inflammation. These findings highlight IGF-2 as a promising target for NMOSD diagnosis and treatment, offering new insights into disease mechanisms and potential interventions.

Supplementary Information: The online version contains supplementary material available at 10.1038/s41598-026-37456-4.

Keywords

AQP4-IgG; Insulin-like growth factor-2; Neuromyelitis optica spectrum disorder; Neuroprotection; Proteomics.

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