ArticleCell reports2015
Activation of necroptosis in multiple sclerosis.
Article in Cell reports, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 331 papers, 1 of them a synthesis that pooled it.
What it found
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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
331 citing papers in PubMed, 1 synthesis or guideline pooled it, 514 citations in OpenAlex.
- Comprehensive analysis of regulated cell death pathways: intrinsic disorder, protein-protein interactions, and cross-pathway communication.Apoptosis : an international journal on programmed cell death · 2025Pooled it
- Safety, Pharmacokinetics and Target Engagement of a Novel Brain Penetrant RIPK1 Inhibitor (SIR9900) in Healthy Adults and Elderly Participants.Clinical and translational science · 2025Trial
- A phase I randomized, double-blinded, placebo-controlled study assessing the safety and pharmacokinetics of RIPK1 inhibitor GFH312 in healthy subjects.Clinical and translational science · 2023Trial
- Safety, pharmacokinetics and target engagement of novel RIPK1 inhibitor SAR443060 (DNL747) for neurodegenerative disorders: Randomized, placebo-controlled, double-blind phase I/Ib studies in healthy subjects and patients.Clinical and translational science · 2022Trial
- Mechanisms, regulation and clinical relevance of necroptosis.Nature reviews. Molecular cell biology · 2026Review
- Review
- DeepFaceMouse enables scalable prediction of large-scale brain activity from facial dynamics in mice.Cell reports methods · 2026Article
- Associations Between Neuromuscular Fatigue, Anxiety, and Peripheral Biomarkers of Neuronal Injury, Inflammation, and Mitochondrial Dysfunction in Treatment-Naïve Relapsing-Remitting Multiple Sclerosis.Brain and behavior · 2026Article
- Integrated Necroptosis Within Programmed Cell Death in Traumatic Brain Injury.Molecular neurobiology · 2026Review
- RIPK 1 in Alzheimer's Disease: Research Progress Integrating Pathogenesis on Necroptosis-Related Neuroinflammation, and Potential Therapeutic Strategies.Biomedicines · 2026Review
- Probing Allosteric Kinase Modulators as Next Game-Changers in Fighting Neurodegeneration.Journal of medicinal chemistry · 2026Review
- Reprogramming gut microenvironment for the treatment of acute severe ulcerative colitis via a synergistic therapy of necroptosis blockade and organoid transplantation.Nature communications · 2026Article
- The RIPK3 Inhibitor GSK872 Attenuates Inflammation and Necroptosis via Modulation of the JNK Signaling Pathway in LPS-Stimulated Microglia.Biomolecules & therapeutics · 2026Article
- TDP-43 pathology triggers neuroinflammation and cognitive impairment by inducing microglial necroptosis.EMBO molecular medicine · 2026Article
- PANoptosis as a drug discovery framework: integrating cell death architecture with clinical translation.Genes and immunity · 2026Review
- Autoimmune neuroinflammation leads to neuronal death via MIF nuclease-mediated parthanatos.Nature neuroscience · 2026Article
- Cell death in multiple sclerosis.Cell death and differentiation · 2026Review
- Targeting necroptosis protects against astrocyte death and hippocampal sclerosis in experimental temporal lobe epilepsy.The Journal of physiology · 2026Article
- Integrated phytochemical, network pharmacology, and computational analysis to elucidate the anti-neurodegenerative mechanisms ofIn silico pharmacology · 2026Article
- Dysregulation of the endosomal sorting complex III is linked to neurodegeneration in progressive multiple sclerosis.Brain pathology (Zurich, Switzerland) · 2026Article
271 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
19 authors at 5 institutions in 2 countries.
Funding
Abstract
Multiple sclerosis (MS), a common neurodegenerative disease of the CNS, is characterized by the loss of oligodendrocytes and demyelination. Tumor necrosis factor α (TNF-α), a proinflammatory cytokine implicated in MS, can activate necroptosis, a necrotic cell death pathway regulated by RIPK1 and RIPK3 under caspase-8-deficient conditions. Here, we demonstrate defective caspase-8 activation, as well as activation of RIPK1, RIPK3, and MLKL, the hallmark mediators of necroptosis, in the cortical lesions of human MS pathological samples. Furthermore, we show that MS pathological samples are characterized by an increased insoluble proteome in common with other neurodegenerative diseases such as Alzheimer's disease (AD), Parkinson’s disease (PD), and Huntington's disease (HD). Finally, we show that necroptosis mediates oligodendrocyte degeneration induced by TNF-α and that inhibition of RIPK1 protects against oligodendrocyte cell death in two animal models of MS and in culture. Our findings demonstrate that necroptosis is involved in MS and suggest that targeting RIPK1 may represent a therapeutic strategy for 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.