ArticleActa neuropathologica communications2018
Systemic inhibition of the membrane attack complex impedes neuroinflammation in chronic relapsing experimental autoimmune encephalomyelitis.
Article in Acta neuropathologica communications, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers.
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Who cites it
30 citing papers in PubMed.
- Role of complement and complement-targeted therapeutics in neurological diseases.Nature reviews. Neurology · 2026Review
- Action of the Terminal Complement Pathway on Cell Membranes.The Journal of membrane biology · 2025Review
- C5aR1 antagonism suppresses inflammatory glial responses and alters cellular signaling in an Alzheimer's disease mouse model.Nature communications · 2024Article
- The complement system in neurodegenerative and inflammatory diseases of the central nervous system.Frontiers in neurology · 2024Review
- Viral-like TLR3 induction of cytokine networks and α-synuclein are reduced by complement C3 blockade in mouse brain.Scientific reports · 2023Article
- Complement activation and increased anaphylatoxin receptor expression are associated with cortical grey matter lesions and the compartmentalised inflammatory response of multiple sclerosis.Frontiers in cellular neuroscience · 2023Article
- Ldlr-/-.Leiden mice develop neurodegeneration, age-dependent astrogliosis and obesity-induced changes in microglia immunophenotype which are partly reversed by complement component 5 neutralizing antibody.Frontiers in cellular neuroscience · 2023Article
- Development, Characterization, and in vivo Validation of a Humanized C6 Monoclonal Antibody that Inhibits the Membrane Attack Complex.Journal of innate immunity · 2023Article
- Editorial: Complement in nervous system disease.Frontiers in cellular neuroscience · 2023Article
- The systemic inhibition of the terminal complement system reduces neuroinflammation but does not improve motor function in mouse models of CMT1A with overexpressedCurrent research in neurobiology · 2023Article
- Brain edema formation and therapy after intracerebral hemorrhage.Neurobiology of disease · 2023Review
- The Complement System in the Central Nervous System: From Neurodevelopment to Neurodegeneration.Biomolecules · 2022Review
- Effects of C5a and Receptor CD88 on Glutamate and N-Methyl-D-Aspartic Acid Receptor Expression in the Mouse Model of Optic Neuromyelitis.Computational and mathematical methods in medicine · 2022Article
- Identification of TLR2 as a Key Target in Neuroinflammation in Vascular Dementia.Frontiers in genetics · 2022Article
- The role of the complement system in Multiple Sclerosis: A review.Frontiers in immunology · 2022Review
- Complement membrane attack complex is an immunometabolic regulator of NLRP3 activation and IL-18 secretion in human macrophages.Frontiers in immunology · 2022Article
- The validity of animal models to explore the pathogenic role of the complement system in multiple sclerosis: A review.Frontiers in molecular neuroscience · 2022Review
- Aberrant Complement System Activation in Neurological Disorders.International journal of molecular sciences · 2021Review
- Review
- The Role of Complement in Synaptic Pruning and Neurodegeneration.ImmunoTargets and therapy · 2021Review
Corrections and comments
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Authors and funding
18 authors.
Funding
Abstract
The complement system is a key driver of neuroinflammation. Activation of complement by all pathways, results in the formation of the anaphylatoxin C5a and the membrane attack complex (MAC). Both initiate pro-inflammatory responses which can contribute to neurological disease. In this study, we delineate the specific roles of C5a receptor signaling and MAC formation during the progression of experimental autoimmune encephalomyelitis (EAE)-mediated neuroinflammation. MAC inhibition was achieved by subcutaneous administration of an antisense oligonucleotide specifically targeting murine C6 mRNA (5 mg/kg). The C5a receptor 1 (C5aR1) was inhibited with the C5a receptor antagonist PMX205 (1.5 mg/kg). Both treatments were administered systemically and started after disease onset, at the symptomatic phase when lymphocytes are activated. We found that antisense-mediated knockdown of C6 expression outside the central nervous system prevented relapse of disease by impeding the activation of parenchymal neuroinflammatory responses, including the Nod-like receptor protein 3 (NLRP3) inflammasome. Furthermore, C6 antisense-mediated MAC inhibition protected from relapse-induced axonal and synaptic damage. In contrast, inhibition of C5aR1-mediated inflammation diminished expression of major pro-inflammatory mediators, but unlike C6 inhibition, it did not stop progression of neurological disability completely. Our study suggests that MAC is a key driver of neuroinflammation in this model, thereby MAC inhibition might be a relevant treatment for chronic neuroinflammatory diseases.
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