Divulging the Intricacies of Crosstalk Between NF-Kb and Nrf2-Keap1 Pathway in Neurological Complications of COVID-19

Bhandari, Ranjana; Khanna, Garima; Kaushik, Dhriti; Kuhad, Anurag

doi:10.1007/s12035-021-02344-7

Cited by 32 publications

(38 citation statements)

References 118 publications

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“…A dramatic ROS production sustains NF-κB pathway, which is accompanied by Nrf2 inactivation, resulting in an amplification of the inflammatory loop. Conversely, a pre-condition of antioxidant Nrf2-dependent redox status or an efficacious recovery of the Nrf2 pathway protects the cells from severe compromising effects [ 153 ].…”

Section: Nrf2 Activation As a Strategy For Covid-19 Treatmentmentioning

confidence: 99%

The Good and Bad of Nrf2: An Update in Cancer and New Perspectives in COVID-19

Emanuele

Celesia

D’Anneo

et al. 2021

IJMS

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Nuclear factor erythroid 2-related factor 2 (Nrf2) is a well-known transcription factor best recognised as one of the main regulators of the oxidative stress response. Beyond playing a crucial role in cell defence by transactivating cytoprotective genes encoding antioxidant and detoxifying enzymes, Nrf2 is also implicated in a wide network regulating anti-inflammatory response and metabolic reprogramming. Such a broad spectrum of actions renders the factor a key regulator of cell fate and a strategic player in the control of cell transformation and response to viral infections. The Nrf2 protective roles in normal cells account for its anti-tumour and anti-viral functions. However, Nrf2 overstimulation often occurs in tumour cells and a complex correlation of Nrf2 with cancer initiation and progression has been widely described. Therefore, if on one hand, Nrf2 has a dual role in cancer, on the other hand, the factor seems to display a univocal function in preventing inflammation and cytokine storm that occur under viral infections, specifically in coronavirus disease 19 (COVID-19). In such a variegate context, the present review aims to dissect the roles of Nrf2 in both cancer and COVID-19, two widespread diseases that represent a cause of major concern today. In particular, the review describes the molecular aspects of Nrf2 signalling in both pathological situations and the most recent findings about the advantages of Nrf2 inhibition or activation as possible strategies for cancer and COVID-19 treatment respectively.

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Section: Nrf2 Activation As a Strategy For Covid-19 Treatmentmentioning

confidence: 99%

The Good and Bad of Nrf2: An Update in Cancer and New Perspectives in COVID-19

Emanuele

Celesia

D’Anneo

et al. 2021

IJMS

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“…For example, Nrf2 inhibits oxidative stress-mediated NF-κB, which decreases free cAMP response element binding protein (CBP), a transcriptional co-activator of Nrf2. In addition, NF-κB regulates the Nrf2-mediated expression of antioxidant response element (ARE) [ 24 , 25 ], and such a crosstalk affects the growth and survival of a malignant tumor [ 26 ]. KEAP1 negatively regulates Nrf2 when it binds to two Kelch subunits in the KEAP1 dimer, and inhibition of the KEAP1-Nrf2 protein–protein interaction could activate Nrf2 [ 27 , 28 ].…”

Section: Resultsmentioning

confidence: 99%

Interaction of (+)-Strebloside and Its Derivatives with Na+/K+-ATPase and Other Targets

Ren

Chen

et al. 2021

Molecules

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Docking profiles for (+)-strebloside, a cytotoxic cardiac glycoside identified from Streblus asper, and some of its derivatives and Na+/K+-ATPase have been investigated. In addition, binding between (+)-strebloside and its aglycone, strophanthidin, and several of their other molecular targets, including FIH-1, HDAC, KEAP1 and MDM2 (negative regulators of Nrf2 and p53, respectively), NF-κB, and PI3K and Akt1, have been inspected and compared with those for digoxin and its aglycone, digoxigenin. The results showed that (+)-strebloside, digoxin, and their aglycones bind to KEAP1 and MDM2, while (+)-strebloside, strophanthidin, and digoxigenin dock to the active pocket of PI3K, and (+)-strebloside and digoxin interact with FIH-1. Thus, these cardiac glycosides could directly target HIF-1, Nrf2, and p53 protein–protein interactions, Na+/K+-ATPase, and PI3K to mediate their antitumor activity. Overall, (+)-strebloside seems more promising than digoxin for the development of potential anticancer agents.

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“…The NF-κB and Nrf2 signaling pathways play a significant role in oxidative stress and cytokine storms, which are the hallmarks of COVID-19 [ 226 ].…”

Section: Resveratrol and Covid-19mentioning

confidence: 99%

“…( h ) In general, genetic intervention and subsequent transcription have a positive effect of the Nrf2 pathway in the reduction of oxidative stress. Infection with COVID-19 causes oxidative stress, which also causes antioxidant benefits associated with Nrf2 [ 226 ]. Figure generated with Biorender ( on 6 September 2021).…”

Section: Figurementioning

confidence: 99%

Resveratrol as an Adjunctive Therapy for Excessive Oxidative Stress in Aging COVID-19 Patients

Liao

et al. 2021

Antioxidants

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The coronavirus disease 2019 (COVID-19) pandemic continues to burden healthcare systems worldwide. COVID-19 symptoms are highly heterogeneous, and the patient may be asymptomatic or may present with mild to severe or fatal symptoms. Factors, such as age, sex, and comorbidities, are key determinants of illness severity and progression. Aging is accompanied by multiple deficiencies in interferon production by dendritic cells or macrophages in response to viral infections, resulting in dysregulation of inflammatory immune responses and excess oxidative stress. Age-related dysregulation of immune function may cause a more obvious pathophysiological response to SARS-CoV-2 infection in elderly patients and may accelerate the risk of biological aging, even after recovery. For more favorable treatment outcomes, inhibiting viral replication and dampening inflammatory and oxidative responses before induction of an overt cytokine storm is crucial. Resveratrol is a potent antioxidant with antiviral activity. Herein, we describe the reasons for impaired interferon production, owing to aging, and the impact of aging on innate and adaptive immune responses to infection, which leads to inflammation distress and immunosuppression, thereby causing fulminant disease. Additionally, the molecular mechanism by which resveratrol could reverse a state of excessive basal inflammatory and oxidative stress and low antiviral immunity is discussed.

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Divulging the Intricacies of Crosstalk Between NF-Kb and Nrf2-Keap1 Pathway in Neurological Complications of COVID-19

Cited by 32 publications

References 118 publications

The Good and Bad of Nrf2: An Update in Cancer and New Perspectives in COVID-19

The Good and Bad of Nrf2: An Update in Cancer and New Perspectives in COVID-19

Interaction of (+)-Strebloside and Its Derivatives with Na+/K+-ATPase and Other Targets

Resveratrol as an Adjunctive Therapy for Excessive Oxidative Stress in Aging COVID-19 Patients

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