Role of NRF2 Pathway in Neurodegenerative Diseases

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: 19 December 2024 | Viewed by 3731

Special Issue Editor


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Guest Editor
1. Instituto de Investigaciones Biomédicas “Sols-Moreale” UAM-CSIC, c/Arturo Duperier 4, 28029 Madrid, Spain
2. Department of Biochemistry, School of Medicine, Universidad Autónoma de Madrid, 28040 Madrid, Spain
3. Institute Teófilo Hernando for Drug Discovery, Universidad Autónoma de Madrid, 28029 Madrid, Spain
4. Centro de Investigación Biomédica en Red de Enfermedades Neurodegenerativas (CIBERNED), Instituto de Salud Carlos III, 28031 Madrid, Spain
Interests: neurodegenerative diseases; NRF2; oxidative stress; neuroinflammation; RNA-binding proteins; mitochondria
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Special Issue Information

Dear Colleagues,

Although the trigger of the neurodegenerative disease process is unknown, the relevance of aging stands out as a major risk for the development of neurodegeneration. With age, a multitude of changes occur at the molecular level, such as an increase in oxidative stress and a decrease in the antioxidant capacity of an organism, with the decrease in the levels of the transcription factor NRF2 being one of the main causes of this imbalance. This creates a favorable environment for the development of neurodegenerative diseases. Although each of these diseases has its own characteristics, they all share altered proteostasis, oxidative stress and neuroinflammation. In recent years, it has been described that the transcription factor NRF2 is involved in the modulation of all these processes, becoming a pleiotropic factor. Therefore, understanding the involvement of NRF2 in the different mechanisms associated with neurodegeneration may be of vital importance in establishing new therapeutic targets.

As Guest Editor, I invite you to contribute to this Special Issue, whose focus will be the role of NRF2 in neurodegenerative disorders.

We also invite researchers in the field and the participants of the COST Action CA20121, Bench to Bedside Transition for Pharmacological regulation of NRF2 in non-communicable diseases (BenBedPhar), to submit their latest research findings to this Special Issue. We look forward to reading your contributions.

Dr. Isabel Lastres-Becker
Guest Editor

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Keywords

  • Alzheimer’s disease
  • Down syndrome
  • frontotemporal dementia
  • Parkinson’s disease
  • Huntington’s disease
  • amyotrophic lateral sclerosis
  • ischemia
  • oxidative stress
  • neuroinflammation
  • proteostasis
  • mitochondria

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Published Papers (2 papers)

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Research

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17 pages, 3351 KiB  
Article
Beneficial Effect of Dimethyl Fumarate Drug Repositioning in a Mouse Model of TDP-43-Dependent Frontotemporal Dementia
by Ignacio Silva-Llanes, Raquel Martín-Baquero, Alicia Berrojo-Armisen, Carmen Rodríguez-Cueto, Javier Fernández-Ruiz, Eva De Lago and Isabel Lastres-Becker
Antioxidants 2024, 13(9), 1072; https://doi.org/10.3390/antiox13091072 - 2 Sep 2024
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Abstract
Frontotemporal dementia (FTD) causes progressive neurodegeneration in the frontal and temporal lobes, leading to behavioral, cognitive, and language impairments. With no effective treatment available, exploring new therapeutic approaches is critical. Recent research highlights the transcription factor Nuclear Factor erythroid-derived 2-like 2 (NRF2) as [...] Read more.
Frontotemporal dementia (FTD) causes progressive neurodegeneration in the frontal and temporal lobes, leading to behavioral, cognitive, and language impairments. With no effective treatment available, exploring new therapeutic approaches is critical. Recent research highlights the transcription factor Nuclear Factor erythroid-derived 2-like 2 (NRF2) as vital in limiting neurodegeneration, with its activation shown to mitigate FTD-related processes like inflammation. Dimethyl fumarate (DMF), an NRF2 activator, has demonstrated neuroprotective effects in a TAU-dependent FTD mouse model, reducing neurodegeneration and inflammation. This suggests DMF repositioning potential for FTD treatment. Until now, no trial had been conducted to analyze the effect of DMF on TDP-43-dependent FTD. In this study, we aimed to determine the potential therapeutic efficacy of DMF in a TDP-43-related FTD mouse model that exhibits early cognitive impairment. Mice received oral DMF treatment every other day from presymptomatic to symptomatic stages. By post-natal day (PND) 60, an improvement in cognitive function is already evident, becoming even more pronounced by PND90. This cognitive enhancement correlates with the neuroprotection observed in the dentate gyrus and a reduction in astrogliosis in the stratum lacunosum-moleculare zone. At the prefrontal cortex (PFC) level, a neuroprotective effect of DMF is also observed, accompanied by a reduction in astrogliosis. Collectively, our results suggest a potential therapeutic application of DMF for patients with TDP-43-dependent FTD. Full article
(This article belongs to the Special Issue Role of NRF2 Pathway in Neurodegenerative Diseases)
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Review

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30 pages, 1521 KiB  
Review
The Role of NRF2 in Trinucleotide Repeat Expansion Disorders
by Kuo-Hsuan Chang and Chiung-Mei Chen
Antioxidants 2024, 13(6), 649; https://doi.org/10.3390/antiox13060649 - 26 May 2024
Cited by 2 | Viewed by 1622
Abstract
Trinucleotide repeat expansion disorders, a diverse group of neurodegenerative diseases, are caused by abnormal expansions within specific genes. These expansions trigger a cascade of cellular damage, including protein aggregation and abnormal RNA binding. A key contributor to this damage is oxidative stress, an [...] Read more.
Trinucleotide repeat expansion disorders, a diverse group of neurodegenerative diseases, are caused by abnormal expansions within specific genes. These expansions trigger a cascade of cellular damage, including protein aggregation and abnormal RNA binding. A key contributor to this damage is oxidative stress, an imbalance of reactive oxygen species that harms cellular components. This review explores the interplay between oxidative stress and the NRF2 pathway in these disorders. NRF2 acts as the master regulator of the cellular antioxidant response, orchestrating the expression of enzymes that combat oxidative stress. Trinucleotide repeat expansion disorders often exhibit impaired NRF2 signaling, resulting in inadequate responses to excessive ROS production. NRF2 activation has been shown to upregulate antioxidative gene expression, effectively alleviating oxidative stress damage. NRF2 activators, such as omaveloxolone, vatiquinone, curcumin, sulforaphane, dimethyl fumarate, and resveratrol, demonstrate neuroprotective effects by reducing oxidative stress in experimental cell and animal models of these diseases. However, translating these findings into successful clinical applications requires further research. In this article, we review the literature supporting the role of NRF2 in the pathogenesis of these diseases and the potential therapeutics of NRF2 activators. Full article
(This article belongs to the Special Issue Role of NRF2 Pathway in Neurodegenerative Diseases)
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