Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Dimethyl fumarate targets in macrophages

ABSTRACT: To understand the molecular mechanism underlying DMF’s inhibition of NLRP3 inflammasome in macrophage, we conducted chemoproteomics to identify the specific protein targets of DMF. We used MMFyne, a previously reported clickable DMF analogue to label and help identify potential DMF target proteins in macrophages.

INSTRUMENT(S):

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Cell Culture, Fibroblast

SUBMITTER: Qin Fu

LAB HEAD: Qin Fu

PROVIDER: PXD063777 | Pride | 2026-05-25

REPOSITORIES: Pride

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
	YandongZhang10461950_YDZ_01262023_MMFynepprofiling_2.mgf	Mgf
	YandongZhang10461950_YDZ_01262023_MMFynepprofiling_2.msf	Msf
	YandongZhang10461950_YDZ_01262023_MMFynepprofiling_2.raw	Raw
	YandongZhang10461950_YDZ_01262023_MMFynepprofiling_r.mgf	Mgf
	YandongZhang10461950_YDZ_01262023_MMFynepprofiling_r.msf	Msf

Items per page:

1 - 5 of 7

Publications

NEK7 Cys298 is important for NLRP3 inflammasome and targetable by dimethyl fumarate.

Zhang Yandong Y Lindner Helena H So Brian B Chen Zirong Z Li Haoyang H Xu Jiashu J Wang Jiahe J Xu Jie J Petre Alexandru M AM Distefano Mark D MD Núñez Gabriel G Lin Hening H

Cell chemical biology 20260421 5

Dimethyl fumarate (DMF), a cysteine targeting agent, is clinically used to treat multiple sclerosis and psoriasis. However, its precise molecular mechanism remains incompletely understood. Here, we investigated the effects of DMF on NLRP3 inflammasome activation. DMF suppresses NLRP3 inflammasome activity at both the priming and activation steps. Using chemoproteomics, we identified DMF targets in macrophages, including IRAK3/4 and RELA/B involved in the NLRP3 priming step, NEK7 involved in NLRP ...[more]

PMID: 42019494

Similar Datasets

Differential neuroprotective and anti-inflammatory effects of dimethyl fumarate, monomethyl fumarate and cannabidiol in neurons and microglia

Project description:Dimethyl fumarate (DMF) is an immunomodulatory treatment for multiple sclerosis (MS) that can cross the blood-brain barrier, presenting neuroprotective potential. Its mechanism of action is not fully understood and there is a need to characterize if DMF or its bioactive metabolite monomethyl fumarate (MMF) exert neuroprotective properties. The combination of adjuvant agents such as cannabidiol (CBD) could be relevant to enhance neuroprotection. The aim of this study was to compare the effects of DMF, MMF and CBD on neuroprotective and immunomodulatory pathways in neurons and microglia in vitro. We found that DMF and CBD, but not MMF, activated the Nrf2 antioxidant pathway in neurons. Similarly, only DMF and CBD, but not MMF, prevented the LPS-induced activation of the inflammatory pathway NF-kB in microglia. However, the 3 drugs inhibited the production of nitric oxide in microglia and protected neurons against apoptosis. Transcriptomically, DMF, MMF and CBD exhibited differential effects on these pathways, with DMF achieving the most pronounced changes. Our results show that DMF and MMF, despite being structurally related, present differences in their mechanisms of action that could be relevant for the achievement of neuroprotection in MS patients and the potential of CBD as an adjuvant therapy in neuroprotection.

2024-09-30 | GSE274435 | GEO

Differential neuroprotective and anti-inflammatory effects of dimethyl fumarate, monomethyl fumarate and cannabidiol in neurons and microglia [Mouse]

2024-09-30 | GSE274859 | GEO

Dimethyl fumarate ameliorates chronic graft-versus-host disease by inhibiting Tfh differentiation via Nrf2

Project description:Chronic graft-versus-host disease (cGVHD), characterized by chronic tissue inflammation and fibrosis involving multiple organs, remains a major complication after allogeneic hematopoietic stem cell transplantation (allo-HSCT). Dimethyl fumarate (DMF) is an anti-inflammatory drug approved for the treatment of multiple sclerosis and psoriasis. We previously reported that DMF effectively inhibits acute GVHD (aGVHD) while preserving the graft-versus-leukemia effect. However, the role of DMF in cGVHD progression remains unknown. Here, we found that DMF administration significantly suppresses follicular helper T cell (Tfh) differentiation, germinal center formation and alleviates disease severity in different murine cGVHD models. Mechanistically, DMF treatment downregulates IL-21 transcription by activation of Nrf2, thus orchestrating Tfh-related gene program both in mice and humans. The inhibitory role of DMF on Tfh cell differentiation was diminished in Nrf2 deficient T cells. Importantly, the therapeutic potential of DMF in clinical cGVHD has been validated in human data whereby DMF effectively reduces IL-21 production and Tfh cell generation in peripheral blood mononuclear cells from active cGVHD patients and further attenuates xenograft GVHD. Collectively, our findings reveal that DMF potently inhibits cGVHD development by repressing Tfh cell differentiation via Nrf2, paving way for the treatment of cGVHD in the clinic.

2024-12-02 | GSE269610 | GEO

Dimethyl Fumarate Mediates Sustained VSMC Remodeling in a Mouse Model of Cerebral Aneurysm

Project description:Cerebral aneurysms (CA) are a type of vascular disease that causes significant morbidity and mortality with rupture. Dysfunction of the vascular smooth muscle cells (VSMCs) from circle of Willis (CoW) vessels mediates CA formation as they are the major cell type of the arterial wall and play a role in maintaining vessel integrity. Dimethyl fumarate (DMF), a first-line oral treatment for relapsing-remitting multiple sclerosis, has been shown to inhibit VSMC proliferation and reduce CA formation in a mouse model. Potential unwanted side effects of DMF on VSMC function have not been investigated yet. The present study characterizes the impact of DMF on VSMC using scRNA-seq in CoW vessels following CA induction and further explores its role in mitochondrial function using in vitro VSMC cultures. Two weeks of DMF treatment following CA induction impaired the transcription of the glutathione redox system and downregulated mitochondrial respiration genes in VSMCs. In vitro, DMF treatment increased lactate formation and enhanced the mitochondrial production of reactive oxygen species (ROS). These effects rendered VSMCs vul-nerable to oxidative stress and led to mitochondrial dysfunction and enhancement of apoptosis. Taken together, our data support the concept that the DMF-mediated antiproliferative effect on VSMCs is linked to disturbed antioxidative functions resulting in altered mitochondrial metabo-lism. This negative impact of DMF treatment on VSMCs may be linked to preexisting alterations of cerebrovascular function due to renal hypertension. Therefore, before severe adverse effects emerge, it would be clinically relevant to develop indices or biomarkers linked to this disturbed antioxidative function to monitor patients undergoing DMF treatment.

2024-06-20 | GSE268079 | GEO

Dimethyl fumarate induces ferroptosis and impairs NF-κB/STAT3 signaling in DLBCL

Project description:Multi-agent chemotherapy still represents the first-line standard-of-care treatment for diffuse large B-cell lymphoma (DLBCL), the most common form of lymphoma in adults. However, the clinicopathological and molecular heterogeneity of DLBCLs poses a major challenge in their successful therapy. At least two major subtypes, i.e. germinal center B-cell-like (GCB) and the aggressive activated B-cell-like (ABC) DLBCL, which differ both in their gene expression profile and in their mutation patterns, have been identified. Here we demonstrate a broad inhibitory effect of dimethyl fumarate (DMF) on the outgrowth of both DLBCL subtypes, even though the molecular basis for its efficacy differs between GCB and ABC DLBCL. Due to high expression of arachidonate 5-lipoxygenase in concert with low glutathione and glutathione peroxidase 4 levels, DMF induced lipid peroxidation and thus ferroptotic cell death in GCB DLBCL. In contrast, in ABC DLBCL inhibition of NF-κB and STAT3 activity essentially contributed to DMF-dependent cytotoxicity. Interestingly, the BCL-2 specific BH3 mimetic ABT-199 or an inhibitor of the ferroptosis suppressor protein 1 synergized with DMF treatment in inducing cell death in DLBCL cell lines. Collectively, our findings identify the established and approved drug DMF as a promising novel therapeutic option in the treatment of both GCB and ABC DLBCL.

2021-07-01 | GSE164267 | GEO

Diet modulates the protective effects of dimethyl fumarate mediated by the immunometabolic neutrophil receptor HCA2

Project description:Monomethyl fumarate (MMF) and its prodrug dimethyl fumarate (DMF) are currently the most widely used agents for the treatment of multiple sclerosis (MS). However, not all patients benefit from DMF. We hypothesized that the variable response of patients may be due to their diet. In support of this hypothesis, mice subjected to experimental autoimmune encephalomyelitis (EAE), a model of MS, did not benefit from DMF treatment when fed a lauric acid-rich (LA) diet, in contrast to normal chow (NC) or, more so, a high-fiber (HFb) diet. DMF lacked efficacy in the LA diet fed group despite similar resorption and preserved effects on plasma lipids. When mice were fed the permissive HFb diet, the protective effect of DMF treatment depended on hydroxycarboxylic receptor 2 (HCA2) which is highly expressed in neutrophil granulocytes. Indeed, deletion of Hca2 in neutrophils abrogated DMF protective effects. Diet had a profound effect on the transcriptional profile of neutrophils and modulated their response to MMF. In summary, DMF required HCA2 on neutrophils as well as permissive dietary effects for its therapeutic action. Translating the dietary intervention into the clinic may improve MS therapy.

2025-05-25 | GSE263752 | GEO

Therapeutic efficacy of dimethyl fumarate in relapsing-remitting multiple sclerosis is linked with monocytic oxidative responses [Illumina]

Project description:Dimethyl fumarate (DMF) is a first-line-treatment for relapsing-remitting multiple sclerosis (RRMS). The redox master regulator Nrf2, essential in redox balance, is a target of DMF, but the precise therapeutic mechanisms remain elusive. Here we show impact of DMF on circulating monocytes and T cells in a prospective longitudinal RRMS patient cohort. DMF increased the level of oxidized isoprostanes in peripheral blood. Other observed changes, including methylome and transcriptome profiles, occur in monocytes prior to T cells. Importantly, monocyte counts and monocytic ROS increase following DMF and distinguish patients with beneficial treatment-response from non-responders. A single nucleotide polymorphism in the ROS-generating NOX3 gene is associated with beneficial DMF treatment-response and suggestively associated with increased ROS generation. Our data implicate monocyte-derived oxidative processes in autoimmune diseases and their treatment, and identify NOX3 genetic variant, monocyte counts and redox state as parameters potentially useful to inform clinical decisions on DMF therapy of RRMS.

2019-07-31 | GSE130491 | GEO

Therapeutic efficacy of dimethyl fumarate in relapsing-remitting multiple sclerosis is linked with monocytic oxidative responses [Affymetrix]

2019-07-31 | GSE130478 | GEO

Transcriptomic profile of multiple sclerosis patients treated with dimethyl fumarate and their age and sex-matched healthy controls

Project description:Dimethyl fumarate (DMF) is an immunomodulatory drug approved for the therapy of multiple sclerosis (MS). The identification of response biomarkers to DMF is a necessity in the clinical practice. With this aim, we studied the transcriptomic changes produced by DMF in peripheral blood mononuclear cells (PBMCs) and its association with clinical response. DMF induced a mild transcriptional effect, with only 328 differentially expressed genes (DEGs) after 12 months of treatment. The overall effect was a downregulation of pro-inflammatory genes, chemokines, and activators of the NF-kB pathway. At baseline, no DEGs were found between responders and non-responders. During DMF treatment a differential transcriptomic response was observed, with responders presenting a higher number of DEGs (902 genes) compared to non-responders (189 genes). Responder patients to DMF exhibit a distinguishable transcriptomic response compared to non-responders that should be further studied for the validation of biomarkers of treatment response to DMF.

2023-08-08 | GSE235357 | GEO

Dimethyl fumarate increases fetal hemoglobin, provides heme detoxification, and corrects anemia in sickle cell disease

Project description:Sickle cell disease (SCD) results from a point mutation in the β-globin gene forming hemoglobin S (HbS), which polymerizes in deoxygenated erythrocytes, triggering recurrent painful vaso-occlusive crises and chronic hemolytic anemia. Reactivation of fetal Hb (HbF) expression ameliorates these symptoms of SCD. Nuclear factor (erythroid derived-2)–like 2 (Nrf2) is a transcription factor that triggers cytoprotective and antioxidant pathways to limit oxidative damage and inflammation and increases HbF synthesis in CD34+ stem cell–derived erythroid progenitors. We investigated the ability of dimethyl fumarate (DMF), a small-molecule Nrf2 agonist, to activate γ-globin transcription and enhance HbF in tissue culture, murine and primate models. DMF recruited Nrf2 to the γ-globin promoters and the locus control region of the β-globin locus in erythroleukemia cells, elevated HbF in SCD donor–derived erythroid progenitors, and reduced hypoxia-induced sickling. Chronic DMF administration in SCD mice induced HbF and increased Nrf2-dependent genes to detoxify heme and limit inflammation. This improved hematological parameters, reduced plasma-free Hb, and attenuated inflammatory markers. Chronic DMF administration to nonanemic primates increased γ-globin mRNA in BM and HbF protein in red cells. DMF represents a potential therapy for SCD to induce HbF and augment vasoprotection and heme detoxification

2017-11-01 | GSE105035 | GEO

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data