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Redox signaling and metabolism in Alzheimer's disease

Reduction and oxidation reactions are essential for biochemical processes. They are part of metabolic pathways and signal transduction. Reactive oxygen species (ROS) as second messengers and oxidative modifications of cysteinyl (Cys) residues are key to transduce and translate intracellular and inte...

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Autores principales: Holubiec, M. I., Gellert, M., Hanschmann, E. M.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9670316/
https://www.ncbi.nlm.nih.gov/pubmed/36408110
http://dx.doi.org/10.3389/fnagi.2022.1003721
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author Holubiec, M. I.
Gellert, M.
Hanschmann, E. M.
author_facet Holubiec, M. I.
Gellert, M.
Hanschmann, E. M.
author_sort Holubiec, M. I.
collection PubMed
description Reduction and oxidation reactions are essential for biochemical processes. They are part of metabolic pathways and signal transduction. Reactive oxygen species (ROS) as second messengers and oxidative modifications of cysteinyl (Cys) residues are key to transduce and translate intracellular and intercellular signals. Dysregulation of cellular redox signaling is known as oxidative distress, which has been linked to various pathologies, including neurodegeneration. Alzheimer's disease (AD) is a neurodegenerative pathology linked to both, abnormal amyloid precursor protein (APP) processing, generating Aβ peptide, and Tau hyperphosphorylation and aggregation. Signs of oxidative distress in AD include: increase of ROS (H(2)O(2), O(2)(•−)), decrease of the levels or activities of antioxidant enzymes, abnormal oxidation of macromolecules related to elevated Aβ production, and changes in mitochondrial homeostasis linked to Tau phosphorylation. Interestingly, Cys residues present in APP form disulfide bonds that are important for intermolecular interactions and might be involved in the aggregation of Aβ. Moreover, two Cys residues in some Tau isoforms have been shown to be essential for Tau stabilization and its interaction with microtubules. Future research will show the complexities of Tau, its interactome, and the role that Cys residues play in the progression of AD. The specific modification of cysteinyl residues in redox signaling is also tightly connected to the regulation of various metabolic pathways. Many of these pathways have been found to be altered in AD, even at very early stages. In order to analyze the complex changes and underlying mechanisms, several AD models have been developed, including animal models, 2D and 3D cell culture, and ex-vivo studies of patient samples. The use of these models along with innovative, new redox analysis techniques are key to further understand the importance of the redox component in Alzheimer's disease and the identification of new therapeutic targets in the future.
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spelling pubmed-96703162022-11-18 Redox signaling and metabolism in Alzheimer's disease Holubiec, M. I. Gellert, M. Hanschmann, E. M. Front Aging Neurosci Aging Neuroscience Reduction and oxidation reactions are essential for biochemical processes. They are part of metabolic pathways and signal transduction. Reactive oxygen species (ROS) as second messengers and oxidative modifications of cysteinyl (Cys) residues are key to transduce and translate intracellular and intercellular signals. Dysregulation of cellular redox signaling is known as oxidative distress, which has been linked to various pathologies, including neurodegeneration. Alzheimer's disease (AD) is a neurodegenerative pathology linked to both, abnormal amyloid precursor protein (APP) processing, generating Aβ peptide, and Tau hyperphosphorylation and aggregation. Signs of oxidative distress in AD include: increase of ROS (H(2)O(2), O(2)(•−)), decrease of the levels or activities of antioxidant enzymes, abnormal oxidation of macromolecules related to elevated Aβ production, and changes in mitochondrial homeostasis linked to Tau phosphorylation. Interestingly, Cys residues present in APP form disulfide bonds that are important for intermolecular interactions and might be involved in the aggregation of Aβ. Moreover, two Cys residues in some Tau isoforms have been shown to be essential for Tau stabilization and its interaction with microtubules. Future research will show the complexities of Tau, its interactome, and the role that Cys residues play in the progression of AD. The specific modification of cysteinyl residues in redox signaling is also tightly connected to the regulation of various metabolic pathways. Many of these pathways have been found to be altered in AD, even at very early stages. In order to analyze the complex changes and underlying mechanisms, several AD models have been developed, including animal models, 2D and 3D cell culture, and ex-vivo studies of patient samples. The use of these models along with innovative, new redox analysis techniques are key to further understand the importance of the redox component in Alzheimer's disease and the identification of new therapeutic targets in the future. Frontiers Media S.A. 2022-11-03 /pmc/articles/PMC9670316/ /pubmed/36408110 http://dx.doi.org/10.3389/fnagi.2022.1003721 Text en Copyright © 2022 Holubiec, Gellert and Hanschmann. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Aging Neuroscience
Holubiec, M. I.
Gellert, M.
Hanschmann, E. M.
Redox signaling and metabolism in Alzheimer's disease
title Redox signaling and metabolism in Alzheimer's disease
title_full Redox signaling and metabolism in Alzheimer's disease
title_fullStr Redox signaling and metabolism in Alzheimer's disease
title_full_unstemmed Redox signaling and metabolism in Alzheimer's disease
title_short Redox signaling and metabolism in Alzheimer's disease
title_sort redox signaling and metabolism in alzheimer's disease
topic Aging Neuroscience
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9670316/
https://www.ncbi.nlm.nih.gov/pubmed/36408110
http://dx.doi.org/10.3389/fnagi.2022.1003721
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