中国神经再生研究(英文版) ›› 2024, Vol. 19 ›› Issue (on line): 1-7.

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Aquaporin-4-IgG-seropositive neuromyelitis optica spectrum disorders: progress of experimental models based on pathogenesis

  

  • 出版日期:2024-01-01 发布日期:2023-11-25

Li Xu*, #, Huiming Xu#, Changyong Tang*   

  1. Department of Neurology, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong Province, China
  • Online:2024-01-01 Published:2023-11-25
  • Contact: Li Xu, MD, xuli36@mail2.sysu.edu.cn; Changyong Tang, PhD, tangchy23@mail.sysu.edu.cn.
  • Supported by:
    This work was supported by grants from the National Natural Science Foundation of China, No. 32100787; Science and Technology Plan Project of Guangzhou City, Nos. 202201020489 and 2023A04J1089 (all to CT).

摘要: https://orcid.org/0000-0002-0370-5108 (Li Xu); https://orcid.org/0000-0001-7048-108X (Changyong Tang)

Abstract: Neuromyelitis optica spectrum disorders (NMOSD) are defined as neuroinflammatory demyelinating disorders that lead to permanent visual loss and motor dysfunction clinically. No effective treatment exists to date, as the exact causative mechanism remains unknown. Therefore, experimental models of neuromyelitis optica spectrum disorders are essential for exploring its pathogenesis and screening for therapeutic targets. Since most neuromyelitis optica spectrum disorder patients are seropositive for IgG autoantibodies against aquaporin-4 highly expressed on the membrane of astrocyte endfeet, most experimental models are developed based on aquaporin-4-IgG that targets astrocytes initially. Current experimental models have successfully simulated many pathologic features of neuromyelitis optica spectrum disorders, such as aquaporin-4 loss, astrocytopathy, granulocyte and macrophage infiltration, complement activation, demyelination, and neuronal loss, but they do not fully capture the pathologic process of human neuromyelitis optica spectrum disorders. In this review, we summarize the currently discovered pathogenic mechanisms and the development of associated experimental models in vitro, ex vivo, and in vivo in neuromyelitis optica spectrum disorders, to suggest potential pathogenic mechanisms for further investigation and provide guidance on experimental model choices. In addition, this review summarizes the latest information on pathologies and therapies for neuromyelitis optica spectrum disorders based on experimental models of aquaporin-4-IgG-seropositive neuromyelitis optica spectrum disorders, offering further therapeutic targets and theoretical basis for clinical trials.

Key words: aquaporin-4, experimental model, neuromyelitis optica spectrum disorder, pathogenesis