2017
DOI: 10.18632/aging.101218
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Abstract: Hallmarks of aging include loss of protein homeostasis and dysregulation of stress-adaptive pathways. Loss of adaptive homeostasis, increases accumulation of DNA, protein, and lipid damage. During acute stress, the Cnc-C (Drosophila Nrf2 orthologue) transcriptionally-regulated 20S proteasome degrades damaged proteins in an ATP-independent manner. Exposure to very low, non-toxic, signaling concentrations of the redox-signaling agent hydrogen peroxide (H2O2) cause adaptive increases in the de novo expression and… Show more

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Cited by 46 publications
(62 citation statements)
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References 112 publications
(62 reference statements)
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“…Moreover, sulforaphane suppresses NRF2-mediated hepatic glucose production and attenuates exaggerated glucose intolerance by an order of magnitude similar to that of metformin in patients with type 2 diabetes mellitus (T2DM) (283). However, forced overexpression of NRF2 might not always be enough to restore adaptive responses (291). For example, the potent NRF2 agonist bardoxolone methyl increases the risk of heart failure compared with placebo in a clinical trial with patients with T2DM and stage 4 CKD (292), which highlights potential limitations of manipulating transcription factors.…”
Section: Box 1: the Cytoprotective Effects Of The Transcription Factomentioning
confidence: 99%
“…Moreover, sulforaphane suppresses NRF2-mediated hepatic glucose production and attenuates exaggerated glucose intolerance by an order of magnitude similar to that of metformin in patients with type 2 diabetes mellitus (T2DM) (283). However, forced overexpression of NRF2 might not always be enough to restore adaptive responses (291). For example, the potent NRF2 agonist bardoxolone methyl increases the risk of heart failure compared with placebo in a clinical trial with patients with T2DM and stage 4 CKD (292), which highlights potential limitations of manipulating transcription factors.…”
Section: Box 1: the Cytoprotective Effects Of The Transcription Factomentioning
confidence: 99%
“…Under normal conditions, Nrf2 is retained cytoplasmically, bound to the cytoskeletal ubiquitin ligase Keap1. Upon stress exposure, Nrf2 releases, translocates to the nucleus, and forms a heterodimer with a small Muscle Aponeurosis Fibromatosis (Maf-S) protein [6] binding to AREs upstream of a battery of antioxidant genes ( Figure 1) including GSTs [7][8][9], carboxylesterases [10], cytochromes p450 [11] and ABC transporters [12] and is involved in regulation of the proteasome, serving to degrade damaged proteins and enzymes following stress-induced damage [13]. In Drosophila the insect Nrf2 ortholog Cap collar isofor C, (CncC), is known to have a central role in both development and the stress response [5,14].…”
Section: Cncc:maf Regulates Insecticide Resistance and Resistance-assmentioning
confidence: 99%
“…Recently, this adaptive response has been revealed to be sex- and age-dependent in Drosophila melanogaster [61]. Nrf2/ Keap-1 axis was also shown to play a key role in stem cell differentiation where ROS levels are constantly altered.…”
Section: Proteasome Systemmentioning
confidence: 99%