ArticleNature communications2021
Wdr1 and cofilin are necessary mediators of immune-cell-specific apoptosis triggered by Tecfidera.
Article in Nature communications, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.
What it found
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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
12 citing papers in PubMed, 40 citations in OpenAlex.
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- Tools to Dissect Lipid Droplet Regulation, Players, and Mechanisms.ACS chemical biology · 2025Review
- Toward decoding spatiotemporal signaling activities of reactive immunometabolites with precision immuno-chemical biology tools.Communications chemistry · 2024Review
- The role of actin cytoskeleton CFL1 and ADF/cofilin superfamily in inflammatory response.Frontiers in molecular biosciences · 2024Review
- The tumor-enriched small molecule gambogic amide suppresses glioma by targeting WDR1-dependent cytoskeleton remodeling.Signal transduction and targeted therapy · 2023Article
- New insights in the targets of action of dimethyl fumarate in endothelial cells: effects on energetic metabolism and serine synthesis in vitro and in vivo.Communications biology · 2023Article
- Z-REX: shepherding reactive electrophiles to specific proteins expressed tissue specifically or ubiquitously, and recording the resultant functional electrophile-induced redox responses in larval fish.Nature protocols · 2023Review
- Finding a vocation for validation: taking proteomics beyond association and location.RSC chemical biology · 2023Review
- Article
- Thyroid Disorders in Patients Treated with Dimethyl Fumarate for Multiple Sclerosis: A Retrospective Observational Study.Antioxidants (Basel, Switzerland) · 2022Article
- Function-guided proximity mapping unveils electrophilic-metabolite sensing by proteins not present in their canonical locales.Proceedings of the National Academy of Sciences of the United States of America · 2022Article
- A primer on harnessing non-enzymatic post-translational modifications for drug design.RSC medicinal chemistry · 2021Article
Corrections and comments
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Authors and funding
7 authors at 5 institutions in 3 countries.
Funding
Abstract
Despite the emerging importance of reactive electrophilic drugs, deconvolution of their principal targets remains difficult. The lack of genetic tractability/interventions and reliance on secondary validation using other non-specific compounds frequently complicate the earmarking of individual binders as functionally- or phenotypically-sufficient pathway regulators. Using a redox-targeting approach to interrogate how on-target binding of pleiotropic electrophiles translates to a phenotypic output in vivo, we here systematically track the molecular components attributable to innate immune cell toxicity of the electrophilic-drug dimethyl fumarate (Tecfidera®). In a process largely independent of canonical Keap1/Nrf2-signaling, Keap1-specific modification triggers mitochondrial-targeted neutrophil/macrophage apoptosis. On-target Keap1-ligand-engagement is accompanied by dissociation of Wdr1 from Keap1 and subsequent coordination with cofilin, intercepting Bax. This phagocytic-specific cell-killing program is recapitulated by whole-animal administration of dimethyl fumarate, where individual depletions of the players identified above robustly suppress apoptosis.
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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.