Metabolic reprogramming in neuromyelitis optica spectrum disorder: From astrocyte dysfunction to immune-mediated...

Neuromyelitis optica spectrum disorders comprise a group of autoimmune diseases of the central nervous system, defined primarily by astrocyte injury mediated by anti-aquaporin-4 antibodies. Although targeted therapies directed against B cells, complement, and inflammatory mediators have substantially reduced the relapse risk in recent years, a subset of patients still exhibits persistent neurological impairment. Recent advances in immunometabolic research suggest that metabolic reprogramming may be a potentially important regulatory process linking immune abnormalities to neurological damage.This review synthesizes the current understanding of metabolic abnormalities and their underlying mechanisms in NMOSD from an immunometabolic perspective, with a particular focus on the interplay between astrocyte damage and disruption of metabolic homeostasis. Current research suggests that AQP4-IgG-mediated astrocyte dysfunction may disrupt the metabolic support network of the central nervous system, which in turn may lead to energy metabolism disorders and mitochondrial dysfunction, and further affect the metabolic state of immune cells. Metabolically reprogrammed T cells and B cells may exhibit functional shifts, which could contribute to the persistence of inflammation and the progression of tissue damage.Among these, metabolic regulatory pathways, including mTOR, AMPK, and HIF-1α, appear to participate in metabolic adaptation and immune regulation across various cell types. Based on these findings, targeting the regulatory networks of glycolysis, mitochondrial homeostasis, and immunometabolic regulation may offer new therapeutic approaches for NMOSD; however, most intervention strategies are still in the experimental exploration phase.Research into metabolic reprogramming in NMOSD remains in its nascent stages. Future investigations, integrating multi-omics approaches and relevant disease models, will be essential to further identify key metabolic targets and to explore the potential synergy between metabolic interventions and existing immunotherapies.