p(HGNC:NFE2L2)

Entity

Name

NFE2L2

Namespace

hgnc

Namespace Version

20180906

Namespace URL

https://raw.githubusercontent.com/pharmacome/terminology/b46b65c3da259b6e86026514dfececab7c22a11b/external/hgnc-names.belns

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

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

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

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

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

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

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

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 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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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