ArticleThe Journal of experimental medicine2008
Aquaporin-4-binding autoantibodies in patients with neuromyelitis optica impair glutamate transport by down-regulating EAAT2.
Article in The Journal of experimental medicine, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 145 papers, 1 of them a synthesis that pooled it.
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Who cites it
145 citing papers in PubMed, 1 synthesis or guideline pooled it, 348 citations in OpenAlex.
- Mechanisms Underlying Aquaporin-4 Subcellular Mislocalization in Epilepsy.Frontiers in cellular neuroscience · 2022Pooled it
- Recognition and management of acute relapse of multiple sclerosis, neuromyelitis optica spectrum disorder and myelin oligodendrocyte glycoprotein antibody-associated disease.Cell death and differentiation · 2026Review
- Ferritin-ApoE nanocarrier for targeted therapy of neuromyelitis optica spectrum disorder in mice.Journal of neuroinflammation · 2026Article
- Aquaporin-4 Dysfunction in Depression: From Pathogenic Mechanisms to Novel Therapeutic Targeting.International journal of molecular sciences · 2026Review
- Why repair fails in AQP4-IgG-positive neuromyelitis optica spectrum disease: an astrocyte-centered framework for remyelination and neuroaxonal preservation.Frontiers in immunology · 2026Review
- Dissecting NMOSD pathogenesis through animal models: a mechanism-oriented systems perspective.Frontiers in immunology · 2026Review
- Inflammatory transcriptomic signatures in a human cellular NMOSD model reveal upregulation of NF-κB and IL6 pathways.Scientific reports · 2025Article
- Innate Immunity in the Pathogenesis of Selected Autoimmune Neurological Diseases.Journal of clinical medicine · 2025Review
- Brain fluid physiology in ischaemic stroke; more than just oedema.Fluids and barriers of the CNS · 2025Review
- Article
- Advances in the treatment of neuromyelitis optic spectrum disorder.Therapeutic advances in neurological disorders · 2025Review
- Oligodendroglia in Neuromyelitis Optica Spectrum Disorder.Advances in neurobiology · 2025Review
- Complement activation in immunological neurological disorders: mechanisms and therapeutic strategies.Frontiers in neurology · 2025Review
- A rare case of systemic lupus erythematosus-associated neuromyelitis optica spectrum disorder with cystic lesions and dual seropositivity for anti-AQP4 and anti-MOG antibodies.Clinical case reports · 2024Article
- Five percent CONeuroprotection (Chichester, England) · 2024Article
- Moving towards a new era for the treatment of neuromyelitis optica spectrum disorders.Journal of neurology · 2024Review
- A Comparative Review of Typical and Atypical Optic Neuritis: Advancements in Treatments, Diagnostics, and Prognosis.Cureus · 2024Review
- Paths to hippocampal damage in neuromyelitis optica spectrum disorders.Neuropathology and applied neurobiology · 2023Article
- T follicular helper cells contribute to pathophysiology in a model of neuromyelitis optica spectrum disorders.JCI insight · 2023Article
- Immuno-pathogenesis of neuromyelitis optica and emerging therapies.Seminars in immunopathology · 2022Review
85 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
9 authors at 2 institutions in 1 country.
Funding
Abstract
Neuromyelitis optica (NMO)-immunoglobulin G (IgG) is a clinically validated serum biomarker that distinguishes relapsing central nervous system (CNS) inflammatory demyelinating disorders related to NMO from multiple sclerosis. This autoantibody targets astrocytic aquaporin-4 (AQP4) water channels. Clinical, radiological, and immunopathological data suggest that NMO-IgG might be pathogenic. Characteristic CNS lesions exhibit selective depletion of AQP4, with and without associated myelin loss; focal vasculocentric deposits of IgG, IgM, and complement; prominent edema; and inflammation. The effect of NMO-IgG on astrocytes has not been studied. In this study, we demonstrate that exposure to NMO patient serum and active complement compromises the membrane integrity of CNS-derived astrocytes. Without complement, astrocytic membranes remain intact, but AQP4 is endocytosed with concomitant loss of Na(+)-dependent glutamate transport and loss of the excitatory amino acid transporter 2 (EAAT2) . Our data suggest that EAAT2 and AQP4 exist in astrocytic membranes as a macromolecular complex. Transport-competent EAAT2 protein is up-regulated in differentiating astrocyte progenitors and in nonneural cells expressing AQP4 transgenically. Marked reduction of EAAT2 in AQP4-deficient regions of NMO patient spinal cord lesions supports our immunocytochemical and immunoprecipitation data. Thus, binding of NMO-IgG to astrocytic AQP4 initiates several potentially neuropathogenic mechanisms: complement activation, AQP4 and EAAT2 down-regulation, and disruption of glutamate homeostasis.
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Registered trials
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.