NRF2 Regulation Processes as a Source of Potential Drug Targets against Neurodegenerative Diseases

Cores, Ángel; Piquero, Marta; Villacampa, Mercedes; León, Rafael; Menéndez, J. Carlos

doi:10.3390/biom10060904

Cited by 60 publications

(66 citation statements)

References 265 publications

(375 reference statements)

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“…Nuclear factor erythroid 2-related factor 2 (Nrf2) is a cytoprotective factor with a protective role against oxidative stress. Nrf2 also regulates the expression of heme oxygenase (HO1), which removes the toxic heme from the cell and plays a protective role against oxidative stress [ 36 , 37 ]. To analyze the effects of lupeol on Nrf2 and HO1, we performed western blot analysis, which showed a reduced expression of Nrf2/HO1 in Aβ 1–42 -induced AD mice brains (cortex and hippocampus) compared to the saline-treated control mice.…”

Section: Resultsmentioning

confidence: 99%

Lupeol, a Plant-Derived Triterpenoid, Protects Mice Brains against Aβ-Induced Oxidative Stress and Neurodegeneration

et al. 2020

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Alzheimer’s disease (AD) is a progressive neurodegenerative disorder that represents 60–70% of all dementia cases. AD is characterized by the formation and accumulation of amyloid-beta (Aβ) plaques, neurofibrillary tangles, and neuronal cell loss. Further accumulation of Aβ in the brain induces oxidative stress, neuroinflammation, and synaptic and memory dysfunction. In this study, we investigated the antioxidant and neuroprotective effects of the natural flavonoid lupeol in the Aβ1–42 mouse model of AD. An Intracerebroventricular injection (i.c.v.) of Aβ (3 µL/5 min/mouse) into the brain of a mouse increased the reactive oxygen species (ROS) levels, neuroinflammation, and memory and cognitive dysfunction. The oral administration of lupeol at a dose of 50 mg/kg for two weeks significantly decreased the oxidative stress, neuroinflammation, and memory impairments. Lupeol decreased the oxidative stress via the activation of nuclear factor erythroid 2-related factor-2 (Nrf-2) and heme oxygenase-1 (HO-1) in the brain of adult mice. Moreover, lupeol treatment prevented neuroinflammation by suppressing activated glial cells and inflammatory mediators. Additionally, lupeol treatment significantly decreased the accumulation of Aβ and beta-secretase-1 (BACE-1) expression and enhanced the memory and cognitive function in the Aβ-mouse model of AD. To the best of our knowledge, this is the first study to investigate the anti-oxidative and neuroprotective effects of lupeol against Aβ1–42-induced neurotoxicity. Our findings suggest that lupeol could serve as a novel, promising, and accessible neuroprotective agent against progressive neurodegenerative diseases such as AD.

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Section: Resultsmentioning

confidence: 99%

Lupeol, a Plant-Derived Triterpenoid, Protects Mice Brains against Aβ-Induced Oxidative Stress and Neurodegeneration

et al. 2020

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“…Nrf2 is a transcriptional factor of the antioxidative enzyme genes including catalase, GPx, GRx, glutathione S-transferase, and SOD. In response to oxidative stress, the Kelch-like ECH-associated protein 1 (KEAP1) inhibits the ubiquitin-proteasome system in the cytosol and facilitates the translocation of Nrf2 into the nucleus to bind to the cis -acting enhancer sequence of the promotor region, the antioxidant response elements [ 184 , 185 ]. Activation of the Nrf2-Keap1 pathway has been observed in various types of cancers, accompanied with reduced antioxidant capacity and elevated oxidative stress and inflammation [ 186 ].…”

Section: Reductive Stressmentioning

confidence: 99%

Monitoring the Redox Status in Multiple Sclerosis

Tanaka

Vécsei

2020

Biomedicines

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Worldwide, over 2.2 million people suffer from multiple sclerosis (MS), a multifactorial demyelinating disease of the central nervous system. MS is characterized by a wide range of motor, autonomic, and psychobehavioral symptoms, including depression, anxiety, and dementia. The blood, cerebrospinal fluid, and postmortem brain samples of MS patients provide evidence on the disturbance of reduction-oxidation (redox) homeostasis, such as the alterations of oxidative and antioxidative enzyme activities and the presence of degradation products. This review article discusses the components of redox homeostasis, including reactive chemical species, oxidative enzymes, antioxidative enzymes, and degradation products. The reactive chemical species cover frequently discussed reactive oxygen/nitrogen species, infrequently featured reactive chemicals such as sulfur, carbonyl, halogen, selenium, and nucleophilic species that potentially act as reductive, as well as pro-oxidative stressors. The antioxidative enzyme systems cover the nuclear factor erythroid-2-related factor 2 (NRF2)-Kelch-like ECH-associated protein 1 (KEAP1) signaling pathway. The NRF2 and other transcriptional factors potentially become a biomarker sensitive to the initial phase of oxidative stress. Altered components of the redox homeostasis in MS were discussed in search of a diagnostic, prognostic, predictive, and/or therapeutic biomarker. Finally, monitoring the battery of reactive chemical species, oxidative enzymes, antioxidative enzymes, and degradation products helps to evaluate the redox status of MS patients to expedite the building of personalized treatment plans for the sake of a better quality of life.

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“…CcpA master regulator of carbon catabolism regulation in Bacillus (Muscariello et al, 2013;Weeks et al, 2012a;Weeks et al, 2012b) LuxR master regulator of quorum sensing (Ball, Chaparian & van Kessel, 2017;Pompeani et al, 2008) WOR1 master regulator of white and opaque phenotypes of Candida albicans (Zhang et al, 2014) P53 master regulator of human malignant tumors (Farnebo, Bykov & Wiman, 2010;Resnick et al, 2005) P63 master regulator of epidermal development and differentiation (Soares & Zhou, 2018) Nrf2 master regulator of redox homeostasis (Basak et al, 2017;Cores et al, 2020;Hayes & Dinkova-Kostova, 2017) MITF master regulator of melanocyte development (Levy, Khaled & Fisher, 2006) TFEB master regulator of lysosomal biogenesis and autophagy (Medina et al, 2015;Settembre et al, 2011) MyoD master regulator of skeletal muscle gene expression programs (Aziz, Liu & Dilworth, 2010;Sunadome et al, 2014) MicroRNAs (miR-10b*,miR21, miR-31,miR153, miR156, etc. ) master regulator of gene expression in many physiological and pathological processes (Biagioni et al, 2012;Datta & Paul, 2015;Kaul & Krams, 2015;Liang et al, 2020;Miranda et al, 2010Schmittgen, 2010Stief et al, 2014;Voorhoeve, 2010) PGC-1 α master regulator of mitochondrial gene expression (Fernandez-Marcos & Auwerx, 2011;Zhu et al, 2009) Prox1 master regulator of lymphatic endothelial cell differentiation (Hong & Detmar, 2003;Kang et al, 2010;Ke & Yang, 2017) AphA master regulator of quorum sensing…”

Section: Related Functionsmentioning

confidence: 99%

“…REST and REST-dependent epigenetic remodeling provide a central mechanism critical to the progressive neuronal degeneration associated with neurologic disorders and diseases including global ischemia, stroke, epilepsy, Alzheimer's and Huntington's disease (Hwang & Zukin, 2018). NRF2 regulation processes as a source of potential drug targets against neurodegenerative diseases (Buendia et al, 2016;Cores et al, 2020). ZCCHC17 is a master regulator of synaptic gene expression in Alzheimer's disease (Tomljanovic et al, 2018).…”

Section: Influence Of Mrgs On Nervous System Diseasesmentioning

confidence: 99%

Master regulator genes and their impact on major diseases

Cai

Zhou

Han

et al. 2020

PeerJ

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Master regulator genes (MRGs) have become a hot topic in recent decades. They not only affect the development of tissue and organ systems but also play a role in other signal pathways by regulating additional MRGs. Because a MRG can regulate the concurrent expression of several genes, its mutation often leads to major diseases. Moreover, the occurrence of many tumors and cardiovascular and nervous system diseases are closely related to MRG changes. With the development in omics technology, an increasing amount of investigations will be directed toward MRGs because their regulation involves all aspects of an organism’s development. This review focuses on the definition and classification of MRGs as well as their influence on disease regulation.

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NRF2 Regulation Processes as a Source of Potential Drug Targets against Neurodegenerative Diseases

Cited by 60 publications

References 265 publications

Lupeol, a Plant-Derived Triterpenoid, Protects Mice Brains against Aβ-Induced Oxidative Stress and Neurodegeneration

Lupeol, a Plant-Derived Triterpenoid, Protects Mice Brains against Aβ-Induced Oxidative Stress and Neurodegeneration

Monitoring the Redox Status in Multiple Sclerosis

Master regulator genes and their impact on major diseases

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