ArticleProceedings of the National Academy of Sciences of the United States of America2017
Autoantibody-induced internalization of CNS AQP4 water channel and EAAT2 glutamate transporter requires astrocytic Fc receptor.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 37 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
37 citing papers in PubMed, 66 citations in OpenAlex.
- 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
- Neutrophil-microglia interaction drives motor dysfunction in a neuromyelitis optica model induced by subarachnoid AQP4-IgG.The Journal of clinical investigation · 2026Article
- The postnatal expression of transcripts and proteins in the corpus callosum, as well as its myelinization, is affected by the congenital absence of AQP4.Journal of physiology and biochemistry · 2026Article
- AQP4-IgG-Induced Astrocyte-Derived Small Extracellular Vesicles Carrying Mitochondrial DNA Regulate the TLR9/MyD88/NF-κB Pathway to Drive Microglial Activation and Neuromyelitis Optica.Neurochemical research · 2026Article
- Aquaporin-4 Dysfunction in Depression: From Pathogenic Mechanisms to Novel Therapeutic Targeting.International journal of molecular sciences · 2026Review
- Astrocyte-intrinsic signaling of chitinase-like protein CHI3L1 drives inflammation and amplifies demyelination in neuromyelitis optica.The Journal of clinical investigation · 2026Article
- PPAR-γ activation by pioglitazone inhibits microglia-mediated neuroinflammation and alleviates disease in neuromyelitis optica spectrum disorders.Acta neuropathologica communications · 2025Article
- Serum Aquaporin-4 Antibody Status and TGF-β in Neuromyelitis Optica Spectrum Disorder: Impact on Astrocyte Function and Correlation with Disease Activity and Severity.Neurology international · 2025Article
- Article
- Complement inhibition rapidly blocks lesion extension and facilitates remyelination in neuromyelitis optica.Acta neuropathologica communications · 2025Article
- Article
- Intravitreal delivery of NMO-IgG causes primary retinal damage in the absence of optic nerve injury.Journal of neuroinflammation · 2025Article
- NaV1.5 autoantibodies in Brugada syndrome: pathogenetic implications.European heart journal · 2024Article
- Bruton's tyrosine kinase-bearing B cells and microglia in neuromyelitis optica spectrum disorder.Journal of neuroinflammation · 2023Article
- Modelling MOG antibody-associated disorder and neuromyelitis optica spectrum disorder in animal models: Spinal cord manifestations.Multiple sclerosis and related disorders · 2023Article
- CHI3L1 signaling impairs hippocampal neurogenesis and cognitive function in autoimmune-mediated neuroinflammation.Science advances · 2023Article
- ACT001 Relieves NMOSD Symptoms by Reducing Astrocyte Damage with an Autoimmune Antibody.Molecules (Basel, Switzerland) · 2023Article
- Spectrum of sublytic astrocytopathy in neuromyelitis optica.Brain : a journal of neurology · 2022Article
- Aquaporin-4 in Neuromyelitis Optica Spectrum Disorders: A Target of Autoimmunity in the Central Nervous System.Biomolecules · 2022Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
5 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Aquaporin-4 (AQP4) water channel-specific IgG distinguishes neuromyelitis optica (NMO) from multiple sclerosis and causes characteristic immunopathology in which central nervous system (CNS) demyelination is secondary. Early events initiating the pathophysiological outcomes of IgG binding to astrocytic AQP4 are poorly understood. CNS lesions reflect events documented in vitro following IgG interaction with AQP4: AQP4 internalization, attenuated glutamate uptake, intramyelinic edema, interleukin-6 release, complement activation, inflammatory cell recruitment, and demyelination. Here, we demonstrate that AQP4 internalization requires AQP4-bound IgG to engage an astrocytic Fcγ receptor (FcγR). IgG-lacking Fc redistributes AQP4 within the plasma membrane and induces interleukin-6 release. However, AQP4 endocytosis requires an activating FcγR's gamma subunit and involves astrocytic membrane loss of an inhibitory FcγR, CD32B. Interaction of the IgG-AQP4 complex with FcγRs triggers coendocytosis of the excitatory amino acid transporter 2 (EAAT2). Requirement of FcγR engagement for internalization of two astrocytic membrane proteins critical to CNS homeostasis identifies a complement-independent, upstream target for potential early therapeutic intervention in NMO.
Indexed as
Identifiers
What OpenQuestion holds
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.