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Appears in Networks 4

In-Edges 31

act(p(FPLX:mTORC1)) increases act(p(HGNC:NFE2L2)) View Subject | View Object

Moreover, the flavonol fisetin stimulated auto- phagic degradation of phosphorylated tau in cortical neu- rons via mTORC1-dependent activation of TFEB and the cytoprotective transcription factor nuclear factor eryth- roid 2-related factor 2 (NFE2L2) 149 . Fisetin also reduced Aβ accumulation in an APP/PS1 mouse model of AD 150 . PubMed:30116051

p(FPLX:AKT) positiveCorrelation p(HGNC:NFE2L2) View Subject | View Object

The second mechanism is related to GSK-3, which phosphorylates NRF2 creating a recognition site for β-Transducin Repeat Containing E3 Ubiquitin Protein Ligase (β-TrCP). β-TrCP leads to Cullin-1/Rbx1-mediated NRF2 ubiquitination and its subsequent degradation [8]. Since GSK-3β is inhibited by phosphorylation at Ser9 by Ser/Thr protein kinases such as AKT, it has been suggested that NRF2 might be up-regulated through activation of AKT and permanent inactivation of GSK-3 [9], [10]. PubMed:29121589

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p(HGNC:GSK3B) decreases p(HGNC:NFE2L2) View Subject | View Object

The second mechanism is related to GSK-3, which phosphorylates NRF2 creating a recognition site for β-Transducin Repeat Containing E3 Ubiquitin Protein Ligase (β-TrCP). β-TrCP leads to Cullin-1/Rbx1-mediated NRF2 ubiquitination and its subsequent degradation [8]. Since GSK-3β is inhibited by phosphorylation at Ser9 by Ser/Thr protein kinases such as AKT, it has been suggested that NRF2 might be up-regulated through activation of AKT and permanent inactivation of GSK-3 [9], [10]. PubMed:29121589

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p(HGNC:GSK3B) decreases p(HGNC:NFE2L2) View Subject | View Object

Nuclear factor erythroid-2-related factor 2 (Nrf2) is a transcription factor known to increase the level of many antioxidants, including glutathione-S transferase (GST), and is negatively regulated by the activity of GSK-3β. Our results indicated the increased nuclear localization of Nrf2 and level of GST, suggesting the increased activity of the transcription factor as a result of GSK-3β suppression, consistent with the decreased oxidative stress observed. Consistent with the improved learning and memory, and consistent with GSK-3b being a tau kinase, we observed decreased tau phosphorylation in brain of GAO-treated SAMP8 mice compared to that of RAO-treated SAMP8 mice. PubMed:24355211

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p(HGNC:NFE2L2, pmod(UbPoly)) increases deg(p(HGNC:NFE2L2)) View Subject | View Object

NRF2 is regulated principally by two different mechanisms. The best established mechanism is the control of protein stability by Kelch-like ECH-associated protein 1 (KEAP1). KEAP1 is an ubiquitin E3 ligase substrate adapter for a Cullin3/Rbx1-dependent E3 ubiquitin ligase complex; henceforth binding of KEAP1 to NRF2 mediates ubiquitination and subsequent proteasomal degradation of NRF2 [7]. PubMed:29121589

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a(CHEBI:"dimethyl fumarate") increases act(p(HGNC:NFE2L2)) View Subject | View Object

The greatest FImax was observed with Protandim at 135-fold, followed by bardoxolone methyl at 67-fold, dimethyl fumarate at 55-fold, and sulforaphane at 21-fold PubMed:22020111

a(CHEBI:"dimethyl fumarate") increases act(p(HGNC:NFE2L2)) View Subject | View Object

When compared contemporaneously in the AREc32-based assay, FImax observed was in the order Protandim > bardoxolone methyl > dimethyl fumarate > sulforaphane. PubMed:22020111

a(CHEBI:"dimethyl fumarate") increases act(p(HGNC:NFE2L2)) View Subject | View Object

A recent laboratory study of dimethyl fumarate found that the compound activates Nrf2 in primary astrocytes, but not in the C6 glioma-derived cell line (Wilms et al., 2010), demonstrating that different cells may respond quite differently to Nrf2 activators PubMed:22020111

a(CHEBI:"dimethyl fumarate") causesNoChange act(p(HGNC:NFE2L2)) View Subject | View Object

A recent laboratory study of dimethyl fumarate found that the compound activates Nrf2 in primary astrocytes, but not in the C6 glioma-derived cell line (Wilms et al., 2010), demonstrating that different cells may respond quite differently to Nrf2 activators PubMed:22020111

a(CHEBI:"dimethyl fumarate") increases act(p(HGNC:NFE2L2)) View Subject | View Object

While Protandim, bardoxolone methyl, BG-12, and sulforaphane all have been demonstrated to modify gene expression profiles by activation of Nrf2, they have not been compared side by side, in the same cell line, under identical conditions. PubMed:22020111

a(CHEBI:resveratrol) decreases act(p(HGNC:NFE2L2)) View Subject | View Object

The study also found that resveratrol, a putative activator of SIRT1 (Howitz et al., 2003), inhibited Nrf2-dependent transcription, apparently contradicting earlier reports that resveratrol activates Nrf2 (Chen et al., 2005; Ungvari et al., 2010). PubMed:22020111

a(CHEBI:sulforaphane) increases act(p(HGNC:NFE2L2)) View Subject | View Object

Sulforaphane is often considered a ‘‘gold standard’’ among naturally-occurring Nrf2 activators (Agyeman et al., 2011). PubMed:22020111

a(CHEBI:sulforaphane) increases act(p(HGNC:NFE2L2)) View Subject | View Object

The greatest FImax was observed with Protandim at 135-fold, followed by bardoxolone methyl at 67-fold, dimethyl fumarate at 55-fold, and sulforaphane at 21-fold PubMed:22020111

a(CHEBI:sulforaphane) increases act(p(HGNC:NFE2L2)) View Subject | View Object

When compared contemporaneously in the AREc32-based assay, FImax observed was in the order Protandim > bardoxolone methyl > dimethyl fumarate > sulforaphane. PubMed:22020111

a(CHEBI:sulforaphane) increases act(p(HGNC:NFE2L2)) View Subject | View Object

While Protandim, bardoxolone methyl, BG-12, and sulforaphane all have been demonstrated to modify gene expression profiles by activation of Nrf2, they have not been compared side by side, in the same cell line, under identical conditions. PubMed:22020111

a(PUBCHEM:135316034) increases act(p(HGNC:NFE2L2)) View Subject | View Object

The greatest FImax was observed with Protandim at 135-fold, followed by bardoxolone methyl at 67-fold, dimethyl fumarate at 55-fold, and sulforaphane at 21-fold PubMed:22020111

a(PUBCHEM:135316034) increases act(p(HGNC:NFE2L2)) View Subject | View Object

When compared contemporaneously in the AREc32-based assay, FImax observed was in the order Protandim > bardoxolone methyl > dimethyl fumarate > sulforaphane. PubMed:22020111

a(PUBCHEM:135316034) increases p(HGNC:NFE2L2) View Subject | View Object

In Alzheimer disease, 66 genes were identified that are also modulated by Protandim at the gene expression level. Of these 66 genes, the first 43 of them (65%) were regulated by Protandim in the opposing direction to that taken by the Alzheimer disease process. The beneficial effect of Protandim is further supported by the fact that of the 10 gene products currently targeted by drug therapies, eight of them are modulated by Protandim in the same direction that is proposed to be beneficial and caused by the drug. PubMed:22020111

a(PUBCHEM:135316034) increases act(p(HGNC:NFE2L2)) View Subject | View Object

While Protandim, bardoxolone methyl, BG-12, and sulforaphane all have been demonstrated to modify gene expression profiles by activation of Nrf2, they have not been compared side by side, in the same cell line, under identical conditions. PubMed:22020111

a(PUBCHEM:400769) increases act(p(HGNC:NFE2L2)) View Subject | View Object

The greatest FImax was observed with Protandim at 135-fold, followed by bardoxolone methyl at 67-fold, dimethyl fumarate at 55-fold, and sulforaphane at 21-fold PubMed:22020111

a(PUBCHEM:400769) increases act(p(HGNC:NFE2L2)) View Subject | View Object

Bardoxolone methyl appeared to produce a biphasic induction, producing near maximal FI over a range of concentrations from less than 40 nM to 0.4 lM PubMed:22020111

a(PUBCHEM:400769) increases act(p(HGNC:NFE2L2)) View Subject | View Object

When compared contemporaneously in the AREc32-based assay, FImax observed was in the order Protandim > bardoxolone methyl > dimethyl fumarate > sulforaphane. PubMed:22020111

a(PUBCHEM:400769) increases act(p(HGNC:NFE2L2)) View Subject | View Object

While Protandim, bardoxolone methyl, BG-12, and sulforaphane all have been demonstrated to modify gene expression profiles by activation of Nrf2, they have not been compared side by side, in the same cell line, under identical conditions. PubMed:22020111

p(HGNC:HMOX1) increases act(p(HGNC:NFE2L2)) View Subject | View Object

HMOX1, induced 56-fold, encodes heme oxygenase-1, an antioxidant enzyme considered a hallmark of Nrf2 activation. PubMed:22020111

path(MESH:"Alzheimer Disease") decreases p(HGNC:NFE2L2) View Subject | View Object

In Alzheimer disease, 66 genes were identified that are also modulated by Protandim at the gene expression level. Of these 66 genes, the first 43 of them (65%) were regulated by Protandim in the opposing direction to that taken by the Alzheimer disease process. The beneficial effect of Protandim is further supported by the fact that of the 10 gene products currently targeted by drug therapies, eight of them are modulated by Protandim in the same direction that is proposed to be beneficial and caused by the drug. PubMed:22020111

path(MESH:"Kidney Diseases") negativeCorrelation act(p(HGNC:NFE2L2)) View Subject | View Object

The study suggests that Nrf2 activation represents a viable new therapeutic approach for renal disease, as similar results are not achievable with currently available therapies PubMed:22020111

path(MESH:"Multiple Sclerosis, Relapsing-Remitting") negativeCorrelation act(p(HGNC:NFE2L2)) View Subject | View Object

These studies suggest that Nrf2 activation may represent a promising new therapeutic approach for multiple sclerosis. PubMed:22020111

bp(GO:"response to oxidative stress") increases p(HGNC:NFE2L2) View Subject | View Object

Oxidative stress abrogates the Keap1-mediated degradation of Nrf2 which in turn accumulates in the nucleus where it heterodimerizes with a small musculoapo- neurotic fibrosarcoma (Maf) protein on antioxidant response elements (AREs) to stimulate the expression of a wide arrays of phase II and antioxidant enzymes including NAD(P)H quinone oxidoreductase 1 (Nqo1), heme oxygenase 1 (Hmox1), glutamane- cysteine ligase (GCL) and glutathione S transferases (GSTs) [84,85,87,88]. PubMed:24563850

act(p(HGNC:KEAP1)) increases deg(p(HGNC:NFE2L2)) View Subject | View Object

Oxidative stress abrogates the Keap1-mediated degradation of Nrf2 which in turn accumulates in the nucleus where it heterodimerizes with a small musculoapo- neurotic fibrosarcoma (Maf) protein on antioxidant response elements (AREs) to stimulate the expression of a wide arrays of phase II and antioxidant enzymes including NAD(P)H quinone oxidoreductase 1 (Nqo1), heme oxygenase 1 (Hmox1), glutamane- cysteine ligase (GCL) and glutathione S transferases (GSTs) [84,85,87,88]. PubMed:24563850

Out-Edges 9

p(HGNC:NFE2L2) positiveCorrelation p(FPLX:AKT) View Subject | View Object

The second mechanism is related to GSK-3, which phosphorylates NRF2 creating a recognition site for β-Transducin Repeat Containing E3 Ubiquitin Protein Ligase (β-TrCP). β-TrCP leads to Cullin-1/Rbx1-mediated NRF2 ubiquitination and its subsequent degradation [8]. Since GSK-3β is inhibited by phosphorylation at Ser9 by Ser/Thr protein kinases such as AKT, it has been suggested that NRF2 might be up-regulated through activation of AKT and permanent inactivation of GSK-3 [9], [10]. PubMed:29121589

Appears in Networks:

p(HGNC:NFE2L2) increases p(ECCODE:"2.5.1.18") View Subject | View Object

Nuclear factor erythroid-2-related factor 2 (Nrf2) is a transcription factor known to increase the level of many antioxidants, including glutathione-S transferase (GST), and is negatively regulated by the activity of GSK-3β. Our results indicated the increased nuclear localization of Nrf2 and level of GST, suggesting the increased activity of the transcription factor as a result of GSK-3β suppression, consistent with the decreased oxidative stress observed. Consistent with the improved learning and memory, and consistent with GSK-3b being a tau kinase, we observed decreased tau phosphorylation in brain of GAO-treated SAMP8 mice compared to that of RAO-treated SAMP8 mice. PubMed:24355211

Appears in Networks:

act(p(HGNC:NFE2L2)) negativeCorrelation path(MESH:"Kidney Diseases") View Subject | View Object

The study suggests that Nrf2 activation represents a viable new therapeutic approach for renal disease, as similar results are not achievable with currently available therapies PubMed:22020111

act(p(HGNC:NFE2L2)) negativeCorrelation path(MESH:"Multiple Sclerosis, Relapsing-Remitting") View Subject | View Object

These studies suggest that Nrf2 activation may represent a promising new therapeutic approach for multiple sclerosis. PubMed:22020111

p(HGNC:NFE2L2) increases bp(HBP:Proteostasis) View Subject | View Object

Moreover, Nrf2 contributes to cellular proteostasis by regulating the expression of molecular chaperones [89], as well as of additional players of proteome stability and maintenance, namely the proteasome subunits [90–92]. PubMed:24563850

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BEL Commons is developed and maintained in an academic capacity by Charles Tapley Hoyt and Daniel Domingo-Fernández at the Fraunhofer SCAI Department of Bioinformatics with support from the IMI project, AETIONOMY. It is built on top of PyBEL, an open source project. Please feel free to contact us here to give us feedback or report any issues. Also, see our Publishing Notes and Data Protection information.

If you find BEL Commons useful in your work, please consider citing: Hoyt, C. T., Domingo-Fernández, D., & Hofmann-Apitius, M. (2018). BEL Commons: an environment for exploration and analysis of networks encoded in Biological Expression Language. Database, 2018(3), 1–11.