Glial-mediated pathogenesis and intervention strategies in neuromyelitis optica spectrum disorder

Neuromyelitis optica spectrum disorder (NMOSD) is a relapsing autoimmune disease primarily characterized by anti-aquaporin-4 immunoglobulin G (AQP4-IgG)-mediated astrocyte injury, neuroinflammation, and demyelination. Glial cells-including astrocytes, microglia, and oligodendrocyte lineage cells-play central roles in NMOSD pathogenesis. Astrocyte loss induced by AQP4-IgG initiates a cascade of immune responses involving microglial activation, proinflammatory cytokine release, and subsequent oligodendrocyte damage. Activated microglia further exacerbate inflammation and tissue injury, while oligodendrocyte dysfunction impairs remyelination. This review summarizes the region-specific distribution and pathological functions of glial cells in NMOSD and highlights their contributions to both lesion formation and repair processes. We also discuss current and emerging therapeutic strategies targeting glial dysfunction, including IL-6 receptor inhibitors, complement blockers, BTK inhibitors, hiPSC-derived glial cell therapies, and microglia-derived exosomes. Understanding the dual roles of glial cells in mediating neuroinflammation and promoting repair offers new insights into disease mechanisms and supports the development of glia-targeted interventions in NMOSD.