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The Role of the Transcription Factor Nrf2 in Alzheimer’s Disease: Therapeutic Opportunities

Alzheimer’s disease (AD) is a common neurodegenerative disorder that affects the elderly. One of the key features of AD is the accumulation of reactive oxygen species (ROS), which leads to an overall increase in oxidative damage. The nuclear factor (erythroid-derived 2)-like 2 (Nrf2) is a master reg...

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Autores principales: De Plano, Laura Maria, Calabrese, Giovanna, Rizzo, Maria Giovanna, Oddo, Salvatore, Caccamo, Antonella
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10046499/
https://www.ncbi.nlm.nih.gov/pubmed/36979483
http://dx.doi.org/10.3390/biom13030549
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author De Plano, Laura Maria
Calabrese, Giovanna
Rizzo, Maria Giovanna
Oddo, Salvatore
Caccamo, Antonella
author_facet De Plano, Laura Maria
Calabrese, Giovanna
Rizzo, Maria Giovanna
Oddo, Salvatore
Caccamo, Antonella
author_sort De Plano, Laura Maria
collection PubMed
description Alzheimer’s disease (AD) is a common neurodegenerative disorder that affects the elderly. One of the key features of AD is the accumulation of reactive oxygen species (ROS), which leads to an overall increase in oxidative damage. The nuclear factor (erythroid-derived 2)-like 2 (Nrf2) is a master regulator of the antioxidant response in cells. Under low ROS levels, Nrf2 is kept in the cytoplasm. However, an increase in ROS production leads to a translocation of Nrf2 into the nucleus, where it activates the transcription of several genes involved in the cells’ antioxidant response. Additionally, Nrf2 activation increases autophagy function. However, in AD, the accumulation of Aβ and tau reduces Nrf2 levels, decreasing the antioxidant response. The reduced Nrf2 levels contribute to the further accumulation of Aβ and tau by impairing their autophagy-mediated turnover. In this review, we discuss the overwhelming evidence indicating that genetic or pharmacological activation of Nrf2 is as a potential approach to mitigate AD pathology.
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spelling pubmed-100464992023-03-29 The Role of the Transcription Factor Nrf2 in Alzheimer’s Disease: Therapeutic Opportunities De Plano, Laura Maria Calabrese, Giovanna Rizzo, Maria Giovanna Oddo, Salvatore Caccamo, Antonella Biomolecules Review Alzheimer’s disease (AD) is a common neurodegenerative disorder that affects the elderly. One of the key features of AD is the accumulation of reactive oxygen species (ROS), which leads to an overall increase in oxidative damage. The nuclear factor (erythroid-derived 2)-like 2 (Nrf2) is a master regulator of the antioxidant response in cells. Under low ROS levels, Nrf2 is kept in the cytoplasm. However, an increase in ROS production leads to a translocation of Nrf2 into the nucleus, where it activates the transcription of several genes involved in the cells’ antioxidant response. Additionally, Nrf2 activation increases autophagy function. However, in AD, the accumulation of Aβ and tau reduces Nrf2 levels, decreasing the antioxidant response. The reduced Nrf2 levels contribute to the further accumulation of Aβ and tau by impairing their autophagy-mediated turnover. In this review, we discuss the overwhelming evidence indicating that genetic or pharmacological activation of Nrf2 is as a potential approach to mitigate AD pathology. MDPI 2023-03-17 /pmc/articles/PMC10046499/ /pubmed/36979483 http://dx.doi.org/10.3390/biom13030549 Text en © 2023 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Review
De Plano, Laura Maria
Calabrese, Giovanna
Rizzo, Maria Giovanna
Oddo, Salvatore
Caccamo, Antonella
The Role of the Transcription Factor Nrf2 in Alzheimer’s Disease: Therapeutic Opportunities
title The Role of the Transcription Factor Nrf2 in Alzheimer’s Disease: Therapeutic Opportunities
title_full The Role of the Transcription Factor Nrf2 in Alzheimer’s Disease: Therapeutic Opportunities
title_fullStr The Role of the Transcription Factor Nrf2 in Alzheimer’s Disease: Therapeutic Opportunities
title_full_unstemmed The Role of the Transcription Factor Nrf2 in Alzheimer’s Disease: Therapeutic Opportunities
title_short The Role of the Transcription Factor Nrf2 in Alzheimer’s Disease: Therapeutic Opportunities
title_sort role of the transcription factor nrf2 in alzheimer’s disease: therapeutic opportunities
topic Review
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10046499/
https://www.ncbi.nlm.nih.gov/pubmed/36979483
http://dx.doi.org/10.3390/biom13030549
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