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Antioxidants
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Nrf2 in Acute and Chronic Neurological Disorders
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Nrf2 in Acute and Chronic Neurological Disorders

A special issue of Antioxidants (ISSN 2076-3921). This special issue belongs to the section "Health Outcomes of Antioxidants and Oxidative Stress".

Deadline for manuscript submissions: closed (30 September 2021) | Viewed by 31210

Special Issue Editor

Prof. Dr. Sylvain Doré

E-Mail Website
Guest Editor
Department of Anesthesiology, Neurology, Psychiatry, and Neuroscience, University of Florida, 1275 Center Drive Gainesville, FL 32610-0254, USA
Interests: acute and chronic neurodegenerative disorders; stroke; vascular cognitive impairment; dementia; Alzheimer’s disease; traumatic brain injury; aging

Special Issue Information

Dear Colleagues, 

There is a lack of effective neuroprotective therapies for both acute and chronic neurological disorders. For example, ischemic stroke accounts for eighty percent of all strokes and is one of the leading causes of death and disability worldwide. Currently, there are no effective treatments for most acute brain insults that demonstrate long-term improvement and recovery. Nrf2 is a transcription factor that aids in regulating cellular and organismal protection and plays a crucial role in firmly controlling redox homeostasis and inflammation in the body. Consequently, the pleiotropic nature of Nrf2 has unique therapeutic potential for the prevention and treatment of both acute and chronic diseases of the central nervous system. The advantage of targeting transcription factor Nrf2 lies in its ability to activate several downstream neuroprotective proteins and enzymes. Such a multipronged approach is likely what is needed to recalibrate brain homeostasis compared to targeting a single and often too simplistic pathway. Nrf2 has been shown to delay necrosis and cell death, reduce cell edema and inflammation, improve function and survival of all cells in the brain, and restore normal flow. It may provide brain resistance against a primary or chronic series of insults. Due to extensive evidence regarding the neuroprotection and benefits of Nrf2 in preclinical models, it is now recommended to test brain-penetrant Nrf2-activating drugs to treat these various neurological deteriorations in rigorous double-blinded clinical trials. 

Prof. Dr. Sylvain Doré
Guest Editor

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Keywords

  • Transcription factor
  • Neuroprotection
  • Nrf2
  • Neurological disorders
  • Stroke
  • Traumatic brain injury
  • Parkinson’s
  • Alzheimer’s

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Published Papers (3 papers)

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Research

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20 pages, 3510 KiB  
Article
Lycopus maackianus Makino MeOH Extract Exhibits Antioxidant and Anti-Neuroinflammatory Effects in Neuronal Cells and Zebrafish Model
by Hwan Lee, Zhiming Liu, Linsha Dong, Sun Hee Cheong and Dong-Sung Lee
Antioxidants 2022, 11(4), 690; https://doi.org/10.3390/antiox11040690 - 31 Mar 2022
Cited by 10 | Viewed by 2651
Abstract
Lycopus maackianus Makino belongs to the Labiatae family and is used in traditional medicine to manage postpartum edema and boils. However, few studies on its antioxidant and anti-inflammatory effects have been conducted. Here, the compounds in L. maackianus methanol (MeOH) extract were profiled [...] Read more.
Lycopus maackianus Makino belongs to the Labiatae family and is used in traditional medicine to manage postpartum edema and boils. However, few studies on its antioxidant and anti-inflammatory effects have been conducted. Here, the compounds in L. maackianus methanol (MeOH) extract were profiled using ultra-high-performance liquid chromatography–time-of-flight high-resolution mass spectrometry analysis. The antioxidant activity of L. maackianus MeOH extract was shown to increase in a concentration-dependent manner by investigating the 2,2-diphenyl-1-picrylhydrazyl and 2,2′-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) radical scavenging activity. Next, in lipopolysaccharide-treated BV2 cells, L. maackianus extract inactivated the nuclear factor-kappa B pathway, inhibiting nitric oxide, prostaglandin E2, interleukin-6, and tumor necrosis factor-α production and inducible nitric oxide synthase and cyclooxygenase-2 protein expression. Furthermore, L. maackianus extract protected against oxidative stress-induced cellular damage in glutamate-stimulated HT22 cells. L. maackianus MeOH extract induced heme oxygenase-1 expression and increased the translocation of nuclear factor E2-related factor 2 in the nucleus, thus exhibiting antioxidant and anti-inflammatory effects. Moreover, the in vivo antioxidant and anti-inflammatory effects of the extract were demonstrated in a zebrafish (Danio rerio) model treated with hydrogen peroxide and lipopolysaccharide. MeOH L. maackianus extract showed antioxidant and anti-neuroinflammatory effects by increasing the expression of heme oxygenase-1, establishing its therapeutic potential for neuroinflammatory diseases. Full article
(This article belongs to the Special Issue Nrf2 in Acute and Chronic Neurological Disorders)
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19 pages, 3267 KiB  
Article
CDDO-Me Attenuates Astroglial Autophagy via Nrf2-, ERK1/2-SP1- and Src-CK2-PTEN-PI3K/AKT-Mediated Signaling Pathways in the Hippocampus of Chronic Epilepsy Rats
by Ji-Eun Kim and Tae-Cheon Kang
Antioxidants 2021, 10(5), 655; https://doi.org/10.3390/antiox10050655 - 23 Apr 2021
Cited by 21 | Viewed by 3127
Abstract
Clasmatodendrosis is an autophagic astroglial death showing extensive swollen cell bodies with vacuoles and disintegrated/beaded processes. This astroglial degeneration is closely relevant to the synchronous epileptiform discharges. However, the underlying molecular mechanisms and the roles of clasmatodendrosis in spontaneous seizure activity are still [...] Read more.
Clasmatodendrosis is an autophagic astroglial death showing extensive swollen cell bodies with vacuoles and disintegrated/beaded processes. This astroglial degeneration is closely relevant to the synchronous epileptiform discharges. However, the underlying molecular mechanisms and the roles of clasmatodendrosis in spontaneous seizure activity are still unknown. The 2-cyano-3,12-dioxo-oleana-1,9(11)-dien-28-oic acid methyl ester (CDDO-Me; RTA 402) is one of the activators for nuclear factor-erythroid 2-related factor 2 (Nrf2) that is a redox-sensitive transcription factor. In the present study, we explored the effects of CDDO-Me on clasmatodendrosis in chronic epilepsy rats, which could prevent epilepsy-related complications. In the present study, clasmatodendritic astrocytes showed reduced Nrf2 expression and its nuclear accumulation, which were restored by CDDO-Me. CDDO-Me also abrogated heat shock protein 25 (HSP25) upregulation in clasmatodendritic astrocytes by regulating extracellular signal-related kinases 1/2 (ERK1/2)-specificity protein 1 (SP1)- and Src-casein kinase 2 (CK2)-phosphatase and tensin homolog deleted on chromosome 10 (PTEN)-phosphatidylinositol-3-kinase (PI3K)-AKT-glycogen synthase kinase 3β (GSK3β)-bax-interacting factor 1 (Bif-1)-mediated signaling pathways in chronic epilepsy rats. In addition, CDDO-Me ameliorated spontaneous seizure duration, but not seizure frequency and behavioral seizure severity. Therefore, our findings suggest that clasmatodendrosis may affect seizure duration in chronic epilepsy rats, and that CDDO-Me may attenuate autophagic astroglial degeneration by regulating various signaling pathways. Full article
(This article belongs to the Special Issue Nrf2 in Acute and Chronic Neurological Disorders)
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Review

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19 pages, 2700 KiB  
Review
Potential Therapeutic Use of the Rosemary Diterpene Carnosic Acid for Alzheimer’s Disease, Parkinson’s Disease, and Long-COVID through NRF2 Activation to Counteract the NLRP3 Inflammasome
by Takumi Satoh, Dorit Trudler, Chang-Ki Oh and Stuart A. Lipton
Antioxidants 2022, 11(1), 124; https://doi.org/10.3390/antiox11010124 - 6 Jan 2022
Cited by 73 | Viewed by 24668
Abstract
Rosemary (Rosmarinus officinalis [family Lamiaceae]), an herb of economic and gustatory repute, is employed in traditional medicines in many countries. Rosemary contains carnosic acid (CA) and carnosol (CS), abietane-type phenolic diterpenes, which account for most of its biological and pharmacological actions, although [...] Read more.
Rosemary (Rosmarinus officinalis [family Lamiaceae]), an herb of economic and gustatory repute, is employed in traditional medicines in many countries. Rosemary contains carnosic acid (CA) and carnosol (CS), abietane-type phenolic diterpenes, which account for most of its biological and pharmacological actions, although claims have also been made for contributions of another constituent, rosmarinic acid. This review focuses on the potential applications of CA and CS for Alzheimer’s disease (AD), Parkinson’s disease (PD), and coronavirus disease 2019 (COVID-19), in part via inhibition of the NLRP3 inflammasome. CA exerts antioxidant, anti-inflammatory, and neuroprotective effects via phase 2 enzyme induction initiated by activation of the KEAP1/NRF2 transcriptional pathway, which in turn attenuates NLRP3 activation. In addition, we propose that CA-related compounds may serve as therapeutics against the brain-related after-effects of SARS-CoV-2 infection, termed “long-COVID.” One factor that contributes to COVID-19 is cytokine storm emanating from macrophages as a result of unregulated inflammation in and around lung epithelial and endovascular cells. Additionally, neurological aftereffects such as anxiety and “brain fog” are becoming a major issue for both the pandemic and post-pandemic period. Many reports hold that unregulated NLRP3 inflammasome activation may potentially contribute to the severity of COVID-19 and its aftermath. It is therefore possible that suppression of NLRP3 inflammasome activity may prove efficacious against both acute lung disease and chronic neurological after-effects. Because CA has been shown to not only act systemically but also to penetrate the blood–brain barrier and reach the brain parenchyma to exert neuroprotective effects, we discuss the evidence that CA or rosemary extracts containing CA may represent an effective countermeasure against both acute and chronic pathological events initiated by SARS-CoV-2 infection as well as other chronic neurodegenerative diseases including AD and PD. Full article
(This article belongs to the Special Issue Nrf2 in Acute and Chronic Neurological Disorders)
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