ArticleJournal of neuroinflammation2019
CD55 upregulation in astrocytes by statins as potential therapy for AQP4-IgG seropositive neuromyelitis optica.
Article in Journal of neuroinflammation, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
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Who cites it
18 citing papers in PubMed, 48 citations in OpenAlex.
- The complement system in Alzheimer's disease: evaluating biomarker potential in a complex neuroimmune context.Journal of neuroinflammation · 2026Review
- Early Transcriptional Changes in Neutrophil-Mediated Processes Following Recanalization After Ischemic Stroke.Journal of the American Heart Association · 2026Article
- Dissecting NMOSD pathogenesis through animal models: a mechanism-oriented systems perspective.Frontiers in immunology · 2026Review
- The complement system in Alzheimer's disease: mechanisms, biomarkers, and therapeutic implications.Frontiers in immunology · 2026Review
- Potential of Natural Products in the Treatment of Glioma: Focus on Molecular Mechanisms.Cell biochemistry and biophysics · 2024Review
- Serum Low-Density Lipoprotein Cholesterol Levels are Associated with Relapse in Neuromyelitis Optica Spectrum Disorder.Journal of inflammation research · 2024Article
- Adipose tissue-derived human mesenchymal stromal cells can better suppress complement lysis, engraft and inhibit acute graft-versus-host disease in mice.Stem cell research & therapy · 2023Article
- Anti-complement Agents for Autoimmune Neurological Disease.Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2022Review
- Targeting the complement system in neuromyelitis optica spectrum disorder.Expert opinion on biological therapy · 2021Review
- Role of complement and potential of complement inhibitors in myasthenia gravis and neuromyelitis optica spectrum disorders: a brief review.Journal of neurology · 2021Review
- Neuromyelitis Optica Spectrum Disorder Treatment-Current and Future Prospects.International journal of molecular sciences · 2021Review
- Statins in Neuro-ophthalmology.Neuro-ophthalmology (Aeolus Press) · 2021Review
- Precision Medicine in Neurology: The Inspirational Paradigm of Complement Therapeutics.Pharmaceuticals (Basel, Switzerland) · 2020Review
- Complementopathies and precision medicine.The Journal of clinical investigation · 2020Review
- Emerging therapeutic targets for neuromyelitis optica spectrum disorder.Expert opinion on therapeutic targets · 2020Review
- Experimental animal models of aquaporin-4-IgG-seropositive neuromyelitis optica spectrum disorders: progress and shortcomings.Brain pathology (Zurich, Switzerland) · 2020Review
- Complement Activation in Association with Markers of Neutrophil Extracellular Traps and Acute Myocardial Infarction in Stable Coronary Artery Disease.Mediators of inflammation · 2020Article
- Triglyceride Level Is an Independent Risk Factor in First-Attacked Neuromyelitis Optica Spectrum Disorders Patients.Frontiers in neurology · 2019Article
Corrections and comments
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Authors and funding
4 authors at 2 institutions in 1 country.
Funding
Abstract
backgroundNeuromyelitis optica spectrum disorder (herein called NMO) is an inflammatory demyelinating disease that can be initiated by binding of immunoglobulin G autoantibodies (AQP4-IgG) to aquaporin-4 on astrocytes, causing complement-dependent cytotoxicity (CDC) and downstream inflammation. The increased NMO pathology in rodents deficient in complement regulator protein CD59 following passive transfer of AQP4-IgG has suggested the potential therapeutic utility of increasing the expression of complement regulator proteins.
methodsA cell-based ELISA was developed to screen for pharmacological upregulators of endogenous CD55 and CD59 in a human astrocyte cell line. A statin identified from the screen was characterized in cell culture models and rodents for its action on complement regulator protein expression and its efficacy in models of seropositive NMO.
resultsScreening of ~ 11,500 approved and investigational drugs and nutraceuticals identified transcriptional upregulators of CD55 but not of CD59. Several statins, including atorvastatin, simvastatin, lovastatin, and fluvastatin, increased CD55 protein expression in astrocytes, including primary cultures, by three- to four-fold at 24 h, conferring significant protection against AQP4-IgG-induced CDC. Mechanistic studies revealed that CD55 upregulation involves inhibition of the geranylgeranyl transferase pathway rather than inhibition of cholesterol biosynthesis. Oral atorvastatin at 10-20 mg/kg/day for 3 days strongly increased CD55 immunofluorescence in mouse brain and spinal cord and reduced NMO pathology following intracerebral AQP4-IgG injection.
conclusionAtorvastatin or other statins may thus have therapeutic benefit in AQP4-IgG seropositive NMO by increasing CD55 expression, in addition to their previously described anti-inflammatory and immunomodulatory actions.
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Registered trials
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