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A natural polyphenol activates and enhances GPX4 to mitigate amyloid-β induced ferroptosis in Alzheimer's disease
Ferroptosis, an iron-dependent cell death, plays a crucial role in the pathology of Alzheimer's disease (AD). Several characteristics of AD, including excessive iron accumulation, elevated lipid peroxide and reactive oxygen species (ROS) levels, and decreased glutathione peroxidase 4 (GPX4) lev...
Autores principales: | , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
The Royal Society of Chemistry
2023
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10498722/ https://www.ncbi.nlm.nih.gov/pubmed/37712018 http://dx.doi.org/10.1039/d3sc02350h |
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author | Baruah, Prayasee Moorthy, Hariharan Ramesh, Madhu Padhi, Dikshaa Govindaraju, Thimmaiah |
author_facet | Baruah, Prayasee Moorthy, Hariharan Ramesh, Madhu Padhi, Dikshaa Govindaraju, Thimmaiah |
author_sort | Baruah, Prayasee |
collection | PubMed |
description | Ferroptosis, an iron-dependent cell death, plays a crucial role in the pathology of Alzheimer's disease (AD). Several characteristics of AD, including excessive iron accumulation, elevated lipid peroxide and reactive oxygen species (ROS) levels, and decreased glutathione peroxidase 4 (GPX4) levels, align with the features of ferroptosis. While traditional methods of inhibiting ferroptosis have centered on chelating Fe and trapping radicals, therapeutic strategies that modulate the GPX4 axis to mitigate ferroptosis in AD are yet to be explored. This report introduces naturally occurring polyphenols (PPs) as dual-acting therapeutic agents to synergistically alleviate ferroptosis and AD. The mechanisms of action encompass modulation of amyloid and tau cascade, reduction of oxidative stress, mitochondrial rescue, and inhibition of ferroptosis. For the first time, we show that a single multifunctional molecule, tannic acid (TA) binds at the activator site of GPX4, augmenting both its activity and cellular levels, providing a conceptually innovative and integrated approach for treating AD via the GPX4–ferroptosis axis. The ability of TA to enhance GPX4 levels under conditions of AD pathology opens up newer promising therapeutic avenues for combating the crosstalk between ferroptosis and AD. |
format | Online Article Text |
id | pubmed-10498722 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | The Royal Society of Chemistry |
record_format | MEDLINE/PubMed |
spelling | pubmed-104987222023-09-14 A natural polyphenol activates and enhances GPX4 to mitigate amyloid-β induced ferroptosis in Alzheimer's disease Baruah, Prayasee Moorthy, Hariharan Ramesh, Madhu Padhi, Dikshaa Govindaraju, Thimmaiah Chem Sci Chemistry Ferroptosis, an iron-dependent cell death, plays a crucial role in the pathology of Alzheimer's disease (AD). Several characteristics of AD, including excessive iron accumulation, elevated lipid peroxide and reactive oxygen species (ROS) levels, and decreased glutathione peroxidase 4 (GPX4) levels, align with the features of ferroptosis. While traditional methods of inhibiting ferroptosis have centered on chelating Fe and trapping radicals, therapeutic strategies that modulate the GPX4 axis to mitigate ferroptosis in AD are yet to be explored. This report introduces naturally occurring polyphenols (PPs) as dual-acting therapeutic agents to synergistically alleviate ferroptosis and AD. The mechanisms of action encompass modulation of amyloid and tau cascade, reduction of oxidative stress, mitochondrial rescue, and inhibition of ferroptosis. For the first time, we show that a single multifunctional molecule, tannic acid (TA) binds at the activator site of GPX4, augmenting both its activity and cellular levels, providing a conceptually innovative and integrated approach for treating AD via the GPX4–ferroptosis axis. The ability of TA to enhance GPX4 levels under conditions of AD pathology opens up newer promising therapeutic avenues for combating the crosstalk between ferroptosis and AD. The Royal Society of Chemistry 2023-08-22 /pmc/articles/PMC10498722/ /pubmed/37712018 http://dx.doi.org/10.1039/d3sc02350h Text en This journal is © The Royal Society of Chemistry https://creativecommons.org/licenses/by-nc/3.0/ |
spellingShingle | Chemistry Baruah, Prayasee Moorthy, Hariharan Ramesh, Madhu Padhi, Dikshaa Govindaraju, Thimmaiah A natural polyphenol activates and enhances GPX4 to mitigate amyloid-β induced ferroptosis in Alzheimer's disease |
title | A natural polyphenol activates and enhances GPX4 to mitigate amyloid-β induced ferroptosis in Alzheimer's disease |
title_full | A natural polyphenol activates and enhances GPX4 to mitigate amyloid-β induced ferroptosis in Alzheimer's disease |
title_fullStr | A natural polyphenol activates and enhances GPX4 to mitigate amyloid-β induced ferroptosis in Alzheimer's disease |
title_full_unstemmed | A natural polyphenol activates and enhances GPX4 to mitigate amyloid-β induced ferroptosis in Alzheimer's disease |
title_short | A natural polyphenol activates and enhances GPX4 to mitigate amyloid-β induced ferroptosis in Alzheimer's disease |
title_sort | natural polyphenol activates and enhances gpx4 to mitigate amyloid-β induced ferroptosis in alzheimer's disease |
topic | Chemistry |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10498722/ https://www.ncbi.nlm.nih.gov/pubmed/37712018 http://dx.doi.org/10.1039/d3sc02350h |
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