Signal amplification in the KEAP1-NRF2-ARE antioxidant response pathway

Liu, Shengnan; Pi, Jingbo; Zhang, Qiang

doi:10.1016/j.redox.2022.102389

Cited by 111 publications

(77 citation statements)

References 150 publications

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“…While a proinflammatory microenvironment might stimulate APP/Aβ accumulation and tau expression with consequent neuronal degeneration, an excessive neuronal inflammation might also trigger a balancing anti-inflammatory response due to the release of inhibitory molecules aiming to reduce neuronal insult (Kinney et al, 2018;Burgaletto et al, 2020). The low NFR2/KEAP1 ratio observed in these Reelin deprived retinas would confirm a shift of the system toward oxidative stress and neuroprotection (Zhan et al, 2021;Liu et al, 2022). In line with Sha and co-workers, the decrease of NRF2 might be responsible for the increased IL6, IL8R and IL18 expressions, as previously described in models of experimental NRF2 deprivation (Saha et al, 2020).…”

Section: Discussionmentioning

confidence: 97%

Morphological and biomolecular targets in retina and vitreous from Reelin-deficient mice (Reeler): Potential implications for age-related macular degeneration in Alzheimer’s dementia

Balzamino

Esposito

Marino

et al. 2022

Front. Aging Neurosci.

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The neurosensory retina is an outgrowth of the Central Nervous System (CNS), and the eye is considered “a window to the brain.” Reelin glycoprotein is directly involved in neurodevelopment, in synaptic plasticity, learning and memory. Consequently, abnormal Reelin signaling has been associated with brain neurodegeneration but its contributing role in ocular degeneration is still poorly explored. To this aim, experimental procedures were assayed on vitreous or retinas obtained from Reeler mice (knockout for Reelin protein) at different postnatal days (p) p14, p21 and p28. At p28, a significant increase in the expression of Amyloid Precursor Protein (APP) and its amyloidogenic peptide (Aβ1-42 along with truncated tau fragment (i.e., NH2htau)- three pathological hallmarks of Alzheimer’s disease (AD)-were found in Reeler mice when compared to their age-matched wild-type controls. Likewise, several inflammatory mediators, such as Interleukins, or crucial biomarkers of oxidative stress were also found to be upregulated in Reeler mice by using different techniques such as ELLA assay, microchip array or real-time PCR. Taken together, these findings suggest that a dysfunctional Reelin signaling enables the expression of key pathological features which are classically associated with AD neurodegenerative processes. Thus, this work suggests that Reeler mouse might be a suitable animal model to study not only the pathophysiology of developmental processes but also several neurodegenerative diseases, such as AD and Age-related Macular Degeneration (AMD), characterized by accumulation of APP and/or Aβ1-42, NH2htau and inflammatory markers.

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Section: Discussionmentioning

confidence: 97%

Morphological and biomolecular targets in retina and vitreous from Reelin-deficient mice (Reeler): Potential implications for age-related macular degeneration in Alzheimer’s dementia

Balzamino

Esposito

Marino

et al. 2022

Front. Aging Neurosci.

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“…NRF2 is regarded as a master mediator for cellular redox homeostasis [ 47 ]. When translocating to the nucleus and combining with a small musculoaponeurotic fibrosarcoma (sMaf), it binds to the promoter regions of antioxidant response elements (AREs) to stimulate the expressions of antioxidants and detoxification enzymes [ 36 ].…”

Section: Discussionmentioning

confidence: 99%

SRT1720 as an SIRT1 activator for alleviating paraquat-induced models of Parkinson's disease

et al. 2022

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“…When Nrf2 exceeds the levels of Keap1, Nrf2 will escape the fixation by Keap1 and translocate into the nucleus, wherein it combines with the small musculoaponeurotic fibrosarcoma (sMaf) proteins to form Nrf2-sMaf heterodimer. The heterodimer recognizes the antioxidant response elements in the promoters of target genes to induce transcription, then performs the antioxidant functions (Liu et al, 2022 ). We found that the Keap1/Nrf2 pathway was inhibited in the colon of osteoarthritic rats, while B. subtilis and E. faecium treatment activated the pathway and increased the entry of Nrf2 into the nucleus.…”

Section: Discussionmentioning

confidence: 99%

Oral administration of live combined Bacillus subtilis and Enterococcus faecium alleviates colonic oxidative stress and inflammation in osteoarthritic rats by improving fecal microbiome metabolism and enhancing the colonic barrier

et al. 2022

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Osteoarthritis (OA) causes intestinal damage. The protective effect of probiotics on the intestine is indeed effective; however, the mechanism of protection against intestinal damage in OA is not clear. In this study, we used meniscal/ligamentous injury (MLI) to mimic OA in rats and explored the colonic protective effects of Bacillus subtilis and Enterococcus faecium on OA. Our study showed that treatment with B. subtilis and E. faecium attenuated colonic injury and reduced inflammatory and oxidative stress factors in the serum of osteoarthritic rats. α- and ß diversity of the fecal flora were not different among groups; no significant differences were observed in the abundances of taxa at the phylum and genus levels. We observed the presence of the depression-related genera Alistipes and Paraprevotella. Analysis of fecal untargeted metabolism revealed that histamine level was significantly reduced in the colon of OA rats, affecting intestinal function. Compared to that in the control group, the enriched metabolic pathways in the OA group were primarily for energy metabolisms, such as pantothenate and CoA biosynthesis, and beta-alanine metabolism. The treatment group had enriched linoleic acid metabolism, fatty acid biosynthesis, and primary bile acid biosynthesis, which were different from those in the control group. The differences in the metabolic pathways between the treatment and OA groups were more evident, primarily in symptom-related metabolic pathways such as Huntington's disease, spinocerebellar ataxia, energy-related central carbon metabolism in cancer, pantothenate and CoA biosynthesis metabolic pathways, as well as some neurotransmission and amino acid transport, and uptake- and synthesis-related metabolic pathways. On further investigation, we found that B. subtilis and E. faecium treatment enhanced the colonic barrier of OA rats, with elevated expressions of tight junction proteins occludin and Zonula occludens 1 and MUC2 mRNA. Intestinal permeability was reduced, and serum LPS levels were downregulated in the treatment group. B. subtilis and E. faecium also regulated the oxidative stress pathway Keap1/Nrf2, promoted the expression of the downstream protective proteins HO-1 and Gpx4, and reduced intestinal apoptosis. Hence, B. subtilis and E. faecium alleviate colonic oxidative stress and inflammation in OA rats by improving fecal metabolism and enhancing the colonic barrier.

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Signal amplification in the KEAP1-NRF2-ARE antioxidant response pathway

Cited by 111 publications

References 150 publications

Morphological and biomolecular targets in retina and vitreous from Reelin-deficient mice (Reeler): Potential implications for age-related macular degeneration in Alzheimer’s dementia

Morphological and biomolecular targets in retina and vitreous from Reelin-deficient mice (Reeler): Potential implications for age-related macular degeneration in Alzheimer’s dementia

SRT1720 as an SIRT1 activator for alleviating paraquat-induced models of Parkinson's disease

Oral administration of live combined Bacillus subtilis and Enterococcus faecium alleviates colonic oxidative stress and inflammation in osteoarthritic rats by improving fecal microbiome metabolism and enhancing the colonic barrier

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