ArticleJCI insight2017
Therapeutic inhibition of soluble brain TNF promotes remyelination by increasing myelin phagocytosis by microglia.
Article in JCI insight, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 54 papers, 1 of them a synthesis that pooled it.
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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.
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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.
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Who cites it
54 citing papers in PubMed, 1 synthesis or guideline pooled it, 109 citations in OpenAlex.
- Current status of neuroprotective and neuroregenerative strategies in multiple sclerosis: A systematic review.Multiple sclerosis (Houndmills, Basingstoke, England) · 2022Pooled it
- Inflammatory bowel disease therapies and demyelinating diseases: a practical guide to therapeutic benefit and risk.Journal of Crohn's & colitis · 2026Review
- Type I Interferon Signaling Augments Autoimmunity in Neuromyelitis Optica Spectrum Disorder.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Multidimensional Engineering of Extracellular Vesicles for Targeted Delivery and Microglial Reprograming in Spinal Cord Injury Repair.ACS nano · 2025Article
- Systemic inhibition of soluble TNF significantly changes glial cell populations leading to improved myelin integrity and better functional outcome after experimental stroke.Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie · 2025Article
- Single intracerebroventricular TNFR2 agonist injection impacts remyelination in the cuprizone model.Journal of molecular medicine (Berlin, Germany) · 2025Article
- Incomplete remyelination via therapeutically enhanced oligodendrogenesis is sufficient to recover visual cortical function.Nature communications · 2025Article
- Phospholipase D Family Member 4 Regulates Microglial Phagocytosis and Remyelination via the AKT Pathway in a Cuprizone-Induced Multiple Sclerosis Mouse Model.CNS neuroscience & therapeutics · 2024Article
- Article
- IKKβ deletion from CNS macrophages increases neuronal excitability and accelerates the onset of EAE, while from peripheral macrophages reduces disease severity.Journal of neuroinflammation · 2024Article
- TNF and TNF receptors as therapeutic targets for rheumatic diseases and beyond.Nature reviews. Rheumatology · 2023Review
- Smouldering Lesion in MS: Microglia, Lymphocytes and Pathobiochemical Mechanisms.International journal of molecular sciences · 2023Review
- Article
- The complex role of inflammation and gliotransmitters in Parkinson's disease.Neurobiology of disease · 2023Review
- Increased Inflammation and Treatment of Depression: From Resistance to Reuse, Repurposing, and Redesign.Advances in neurobiology · 2023Article
- Remyelination in Multiple Sclerosis: Findings in the Cuprizone Model.International journal of molecular sciences · 2022Review
- Article
- Siponimod Modulates the Reaction of Microglial Cells to Pro-Inflammatory Stimulation.International journal of molecular sciences · 2022Article
- Characterization of Glial Populations in the Aging and Remyelinating Mouse Corpus Callosum.Neurochemical research · 2022Article
- Elevated TNF-α Leads to Neural Circuit Instability in the Absence of Interferon Regulatory Factor 8.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2022Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
7 authors at 5 institutions in 4 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Multiple sclerosis (MS) is an inflammatory CNS demyelinating disease in which remyelination largely fails. Transmembrane TNF (tmTNF) and TNF receptor 2 are important for remyelination in experimental MS models, but it is unknown whether soluble TNF (solTNF), a major proinflammatory factor, is involved in regeneration processes. Here, we investigated the specific contribution of solTNF to demyelination and remyelination in the cuprizone model. Treatment with XPro1595, a selective inhibitor of solTNF that crosses the intact blood-brain barrier (BBB), in cuprizone-fed mice did not prevent toxin-induced oligodendrocyte loss and demyelination, but it permitted profound early remyelination due to improved phagocytosis of myelin debris by CNS macrophages and prevented disease-associated decline in motor performance. The beneficial effects of XPro1595 were absent in TNF-deficient mice and replicated in tmTNF-knockin mice, showing that tmTNF is sufficient for the maintenance of myelin and neuroprotection. These findings demonstrate that solTNF inhibits remyelination and repair in a cuprizone demyelination model and suggest that local production of solTNF in the CNS might be one reason why remyelination fails in MS. These findings also suggest that disinhibition of remyelination by selective inhibitors of solTNF that cross the BBB might represent a promising approach for treatment in progressive MS.
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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.