ArticleProceedings of the National Academy of Sciences of the United States of America2012
Molecular outcomes of neuromyelitis optica (NMO)-IgG binding to aquaporin-4 in astrocytes.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 167 papers.
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Who cites it
167 citing papers in PubMed, 323 citations in OpenAlex.
- Long-Term Safety and Efficacy of Eculizumab in Aquaporin-4 IgG-Positive NMOSD.Annals of neurology · 2021Trial
- Spatial organization of AQP4 water channel expression in the human brain.Science advances · 2026Article
- The cascade to pathogenicity in autoantibody-mediated CNS diseases.Brain : a journal of neurology · 2026Review
- The Comprehensive Live Cell-Based Cytotoxicity Assay for Monitoring Disease Activity and Guiding Rescue Therapy in Acute Attacks of NMOSD.Annals of clinical and translational neurology · 2026Article
- Dynamic characterization of pathological and functional deterioration in a mouse model of optic neuritis related to neuromyelitis optica spectrum disorder.Neural regeneration research · 2026Article
- Natalizumab exacerbates astrocytopathy in NMOSD via blockade of endothelial VCAM1-astrocytic integrin α4 interaction.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- Neuromyelitis optica spectrum disorder overlapping with Sjögren's disease: immunopathological links and therapeutic implications.Frontiers in immunology · 2026Review
- Inflammatory transcriptomic signatures in a human cellular NMOSD model reveal upregulation of NF-κB and IL6 pathways.Scientific reports · 2025Article
- Review
- Sleep and Risk of Multiple Sclerosis: Bridging the Gap Between Inflammation and Neurodegeneration via Glymphatic Failure.Brain sciences · 2025Review
- Neuro-immune crosstalk in cancer: mechanisms and therapeutic implications.Signal transduction and targeted therapy · 2025Review
- Structural basis of aquaporin-4 autoantibody binding in neuromyelitis optica.Science advances · 2025Article
- Toward curing neurological autoimmune disorders: Biomarkers, immunological mechanisms, and therapeutic targets.Neuron · 2025Review
- Complement activation in immunological neurological disorders: mechanisms and therapeutic strategies.Frontiers in neurology · 2025Review
- Selected Aspects of the Neuroimmunology of Cell Therapies for Neurologic Disease: Perspective.Neurology(R) neuroimmunology & neuroinflammation · 2025Review
- B cell depletion as a therapeutic strategy for neuromyelitis optica spectrum disorder: rationale, evidence, and challenges.Frontiers in immunology · 2025Review
- Article
- Moving towards a new era for the treatment of neuromyelitis optica spectrum disorders.Journal of neurology · 2024Review
- Network Meta-analysis of Ravulizumab and Alternative Interventions for the Treatment of Neuromyelitis Optica Spectrum Disorder.Neurology and therapy · 2024Review
- Structural Basis of Aquaporin-4 Autoantibody Binding in Neuromyelitis Optica.bioRxiv : the preprint server for biology · 2024Article
107 more citing papers are in PubMed but not listed here.
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Authors and funding
9 authors at 2 institutions in 2 countries.
Funding
Abstract
The astrocytic aquaporin-4 (AQP4) water channel is the target of pathogenic antibodies in a spectrum of relapsing autoimmune inflammatory central nervous system disorders of varying severity that is unified by detection of the serum biomarker neuromyelitis optica (NMO)-IgG. Neuromyelitis optica is the most severe of these disorders. The two major AQP4 isoforms, M1 and M23, have identical extracellular residues. This report identifies two novel properties of NMO-IgG as determinants of pathogenicity. First, the binding of NMO-IgG to the ectodomain of astrocytic AQP4 has isoform-specific outcomes. M1 is completely internalized, but M23 resists internalization and is aggregated into larger-order orthogonal arrays of particles that activate complement more effectively than M1 when bound by NMO-IgG. Second, NMO-IgG binding to either isoform impairs water flux directly, independently of antigen down-regulation. We identified, in nondestructive central nervous system lesions of two NMO patients, two previously unappreciated histopathological correlates supporting the clinical relevance of our in vitro findings: (i) reactive astrocytes with persistent foci of surface AQP4 and (ii) vacuolation in adjacent myelin consistent with edema. The multiple molecular outcomes identified as a consequence of NMO-IgG interaction with AQP4 plausibly account for the diverse pathological features of NMO: edema, inflammation, demyelination, and necrosis. Differences in the nature and anatomical distribution of NMO lesions, and in the clinical and imaging manifestations of disease documented in pediatric and adult patients, may be influenced by regional and maturational differences in the ratio of M1 to M23 proteins in astrocytic membranes.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.